Notes on This Category

These herbs promote proper circulation and dispel stasis for the recovery of normal blood circulation. According to Guohui Liu, with normal use, they will not move blood in an aberrant manner (with a few possible exceptions). Most of the herbs in the category are not anticoagulants.

Commonly combined with:
A. Herbs that warm the interior and disperse cold when blood stagnation is caused by cold obstruction.
B. Herbs that clear heat and cool the blood when blood stasis is due to congealing of the blood by heat.
C. Herbs that eliminate wind, cold, and damp when the channels are obstructed by invasion of these factors.
D. Qi tonics when Qi is deficient, and also to protect the Qi from damage by these herbs.
E. Blood tonics when blood is deficient, and also to protect the blood from damage by these herbs.
F. Herbs that resolve phlegm when blood stasis is caused by phlegm.

Other Herbs that Promote Proper Blood Circulation, to Consider When Appropriate:
An Xi Xiang [Open Orifices], Bie Jia [Nourish Yin], Chi Shao [Cool Blood], Da Huang [Promote BM], Dang Gui [Nourish Blood], Du Huo [Dispel Wind-Damp], Fu Zi [Warm Interior], Gu Sui Bu [Tonify Yang], Gui Zhi [Acrid, Warm], He Huan Pi [Calm Shen], Hong Teng [Clear Heat & Toxicity], Jing Jie Tan (charred) [Acrid, Warm], Lu Jiao [Tonify Yang], Mu Dan Pi [Cool Blood], Mu Tong [Drain Damp], Pu Huang [Stop Bleeding], Qian Cao Gen [Stop Bleeding], San Qi [Stop Bleeding], She Xiang [Open Orifices], Wa Leng Zi [Topical Herbs], Xie Bai [Move Qi], Xu Duan [Tonify Yang], Xue Yu Tan [Stop Bleeding], Xue Jia [Topical Herbs], Zao Jiao Ci [Resolve Phlegm], Zi Cao [Cool Blood].

Chuan Shan Jia – Pangolin scales – “Penetrate Mountain Scales”

Nature: salty, slightly cold

Enters: Liver, Stomach

Actions: Promotes blood circulation and dispels blood stasis from the channels; promotes lactation; relieves swelling; drains pus; unblocks menstruation; expels wind-dampness from the channels.

Indications:
• Pangolins are threatened (some species endangered). Attempts to raise them in captivity have failed. You can get the job done with another medicine.
• Blood stasis: amenorrhea, masses, Bi syndrome, early stage carbuncles/boils or with pus that does not drain, lumps, dysmenorrhea, lack of or insufficient lactation.
• Galactostasis after childbirth.
• Toxic swellings: abscesses, boils. Can dissolve as yet unformed pus, but it is more useful for suppurative lesions. Can be used topically.
• Wind-damp obstruction of channels: pain, stiffness or spasms in the limbs, pain that prevents bending and stretching.
• When the patient lacks breast milk and is Qi deficient, do not count on this herb to promote lactation.
• Excellent success as a hemostatic in surgery.
• May be useful for the treatment of hematuria.
• May raise WBC count.
• Traditionally this herb is powdered and taken directly. Too expensive to cook.
• Contraindicated in pregnancy.
• Liu: This herb can go anywhere in the body, and conducts other herbs to the appropriate area.
• The unprepared form is black. The prepared form has been fried until yellowish.
• Though sometimes referred to as “anteaters,” pangolins are not true anteaters.
HF: A Sha Chong (kill worms or parasites) herb, important in Gu Zheng (Gu parasites) formulas.
BF: Useful when there is concomitant damp-heat. Stasis with damp and heat is very common in women with endometriosis.

Dose: 3-9g

Chuan Xiong – Ligusticum root – Szechuan Lovage – Cnidium

Nature: acrid, warm

Enters: Pericardium, Liver, Gallbladder

Actions: Promotes blood and Qi circulation; eliminates external wind; relieves pain; moves Qi upward.

Indications:
• Blood (and Qi) stasis: irregular menstruation, amenorrhea, difficult labor, lochioschesis, and many kinds of pain, including abdominal, chest, flank, hypochondriac, dysmenorrhea, pain from traumatic injury, pain from carbuncles and boils, headaches, Bi syndrome.
• External wind disorders: headache, dizziness, painful obstructions, skin disorders; wind-damp arthritis/rheumatism.
• Reaches from the head down to the sea of blood.
• For a variety of wind patterns (wind-cold, wind-heat, wind-dampness, etc.) depending on the herbs it is combined with.
• Overdose may cause vomiting and dizziness.
Hsu: Antispasmodic, analgesic: inhibits intestinal and uterine contraction; slightly hypotensive; tranquilizer (essential oil); antibacterial, antifungal.
DY: Treats the Qi within the blood; dispels stasis; in the upper body, it goes toward the head and the eyes; in the lower body it goes toward the sea of blood (uterus [“Sea of Blood” may also indicate the Chong Mai or liver]); drying.
• For wind-cold (headache, etc.), use the uncooked form.
• For menstrual problems, pain, and inflammations, use the wine-processed form.
• With Dang gui to move the Qi and quicken the blood without damaging the blood, to nourish the blood without producing stasis, to dispel stasis and stop pain. For the following indications, both herbs should be wine-processed, though uncooked Chuan xiong may be used in the case of headaches or dermatological problems:
– 1. Menstrual irregularities, dysmenorrhea, and postpartum abdominal pain due to blood stasis that may be mixed with Qi stagnation. (Xiong Gui San)
– 2. Rheumatic pain due to wind-dampness and blood vacuity.
– 3. Headaches due to blood deficiency and/or blood stasis. (Jia Wei Si Wu Tang)
– 4. Wounds, ulcers, or enduring cutaneous inflammations due to Qi and blood vacuity with Qi and blood stagnation. (Tou Nong San)
• With Shi gao to dispel wind, clear and drain heat, quicken the blood and move the Qi, and stop pain. For headaches due to wind-heat or full heat (particularly that which is located in the Shaoyang or Jueyin channels). Use unprepared Chuan xiong. For wind-heat headaches, add herbs that dispel wind.
• Headaches: Chuan xiong is mainly used for wind-dampness and wind-cold headaches. However, it can be used for all kinds of headaches if combined appropriately. For wind-damp, add Qiang huo and Bai zhi. For wind-cold, add Fang feng and Jing jie. For wind-heat, add Ju hua and Bo he. For blood stasis, add Hong hua and Yan hu suo. For blood deficiency, add Dang gui and Ji xue teng. For full heat, add Shi gao and Zhi mu. For Qi stagnation, add Chai hu and Bai ji li. For liver Yang hyperactivity, add Tian ma and (Huai) Niu xi.
Weng Weiliang, et al: This herb is indicated in the treatment of headache, rheumatic arthralgia, abdominal pain with mass formation, pricking pain in the costal regions, swelling and pain due to traumatic injury, arthralgia due to cold, spasm of tendons, menstrual disorders, amenorrhea, dysmenorrhea.
HF: An important herb in anti-Gu therapy to move Qi (xing Qi) and break accumulation (po ji).
SD: Chuanxiong is a frequently used Chinese herb, commonly called ligusticum or cnidium. The latter name is the term most often used in the ITM literature, adopted from the common name offered by Oriental Healing Arts Institute (OHAI) in publications 30 years ago. The herb has been obtained from Ligusticum chuanxiong (= Ligusticum wallichii) in China and from Cnidium officinale in Japan; the OHAI literature was heavily influenced by Japanese herb scholars. Recent evaluation of the genetic material of these two source materials has led to the suggestion that they are, in fact, the same plant, and that Cnidium officinale should be renamed as Ligusticum chuanxiong (1).
There are several active constituents in chuanxiong, but one of the most interesting is the alkaloid ligustrazine, which has the chemical name tetramethylpyrazine (because it is a pyrazine ring with four symmetrically placed methyl groups); it is sometimes simply called TMP. Isolated alkaloids from chuanxiong, and purified synthetic ligustrazine, have been used in China as medicinal agents for 30 years. The initial applications were based on traditional uses of the crude herb in decoctions and pills: for vitalizing blood circulation in the treatment of cardiovascular diseases
and for treatment of headache and vertigo.
LIGUSTRAZINE BY IV ADMINISTRATION
Ligustrazine is rapidly absorbed when taken orally, but it is also rapidly excreted in the urine. In order to maintain high blood levels, oral doses must be taken every few hours. Alternatively, ligustrazine can be given by IV drip over several hours to keep the blood levels high. Such administration is typical for hospitalized patients in China who have suffered heart attack or stroke and for treatment of serious childhood diseases (it is administered to infants who can not swallow herbal decoctions or pills). However, for most non-emergency uses, the IV form of administration is not convenient; further, it is not routinely available outside of China. Still, the IV use of this compound over the past three decades, both for adults and children, illustrates the lack of toxicity from TMP.
LIGUSTRAZINE BY ORAL ADMINISTRATION
Ligustrazine as a component of chuanxiong is only present in small amounts, perhaps 1%, so that a 9-12 gram quantity of the crude herb in decoction (as might be used in modern clinical practice in China) yields about 90 mg-120 mg of ligustrazine for a one-day dose. While this quantity may provide some benefits, contributing one active component to a complex mixture, it is not adequate to get the full benefit of ligustrazine that has been described in clinical and laboratory work with the isolated compound. Oral dosing of 100 mg or more each time, at least three times a day would be necessary to get sufficient blood levels for the desired effects.
To enhance the action of ligustrazine, even when given in adequate dosage, Chinese doctors often combine it with one or more herbs that have the related therapeutic action of vitalizing blood. The main herb used in combination with ligustrazine is salvia, either alone or with tang-kuei.
APPLICATIONS
The applications of ligustrazine in China are many, and at first may appear quite diverse. However, upon examining the various applications, one can appreciate ligustrazine as providing a “protective effect.” Following are brief reviews of a few of the uses of ligustrazine.
Renal failure and dialysis: Ligustrazine has been used to slow or halt the progress of renal failure in Chinese patients (2). Experimental studies have been conducted to demonstrate this effect in laboratory animals (3). One of the proposed mechanisms is the superoxide scavenging effect, one type of antioxidant action (4). Salvia has also been used to protect against renal failure (see ITM review: The use of salvia for patients with renal failure). Ligustrazine with salvia and tang-kuei have been used to aid patients undergoing renal dialysis (5). TMP is also used in conjunction with prednisone for patients with primary nephritic syndrome, which is said to function better than prednisone therapy alone (6). In the treatment of infants, ligustrazine was used to protect against the renal toxicity of gentamycin (7). Ferulic acid, possibly the primary active component of tang-kuei and one of the active components of chuanxiong, has shown benefits for treatment of patients with diabetic nephropathy (8).
Lung diseases with fibrosis: Ligustrazine is known to be a pulmonary vasodilator (9), but an area of particular interest is its action to protect against pulmonary fibrosis (10). Salvia and an active fraction of salvia (labeled IH764-3) have also been used for protection against pulmonary fibrosis (11-13), alone or with ligustrazine.
Neuroprotection for stroke: Chinese physicians have used chuanxiong and ligustrazine for treatment of stroke patients. Ligustrazine has been shown to have protective effects for the neurons, possibly based on anti-inflammatory activity (14-15). In clinical applications, ligustrazine in high dosage (480 mg/day) was found to lower fibrinogen and improve blood circulation in patients who suffered a stroke (16). Salvia is also known to confer neuroprotective effects in case of stroke (see review article: Neuroprotective herbs and active ingredients). Ferulic acid or its sodium salt (sodium ferulate) is used in Chinese medicine to treat stroke patients; in laboratory studies, it was shown to limit damage and help reactivation of impaired nerve cells (17).
In sum, ligustrazine alone or with salvia may provide protection to the kidneys, lungs, and brain through antioxidant and anti-inflammatory effects; these substances reduce fibrosis and improve blood circulation. The addition of tang-kuei, especially as a good source of ferulic acid (see structure, below), may further improve the effects.

Dose: 3-10g

Dan Shen – Salvia miltiorrhiza root – Red Sage – “Cinnabar Root”

Nature: bitter, slightly cold

Enters: Heart, Pericardium, Liver

Actions: Promotes blood circulation and dispels blood stasis; cools the blood; relieves swelling; mildly nourishes blood; calms the Shen; unblocks the menses.

Indications:
• Blood stasis: irregular menstruation, amenorrhea, abdominal pain after childbirth, pain in the chest, abdomen, epigastrium, masses and pain in the limbs, lochioschesis.
• Blood stasis with liver Qi stagnation: pain in the ribs or hypochondria.
• Heat in the blood and blood stasis: carbuncles, boils.
• Febrile disease (including Ying level): restlessness, delirium, high fever, eruptions, red tongue.
• Heat and blood stasis in the heart: insomnia, palpitations, irritability, restlessness. Also for heart/kidney Yin deficiency heat patterns.
• Primary herb for coronary heart disease in China. (Particularly in combination with San qi, Gui zhi, Shan zha, etc.)
• For immune system disorders Liu combines with Dang gui.
• For CNS-mediated pain, including post-stroke, combine with Huang qi in doses of 15-30g of each (when Qi deficiency and blood stasis are present)
• Promotes tissue regeneration; opens coronary arteries; reduces blood sugar; reduces serum cholesterol; protects the liver; enhances the immune system; vasodilator; relieves angina pectoris.
• Wine-frying the herb enhances its blood circulating properties.
• This herb can be compared to the formula Si Wu Tang, though Dan shen is weaker at nourishing blood and stronger at moving blood than Si Wu Tang.
• Do not use large doses in patients predisposed to bleeding.
• Note: the Salvia genus contains many herbs with drastically different properties – e.g., culinary sage – Salvia officinalis (also a diaphoretic), and the hallucinogenic drug Salvia divinorum. “Salvia” alone is not a sufficient name.
BII: May improve visual acuity in glaucoma.
MLT: Regulates cholesterol, triglycerides. Premiere herb for heart problems, especially angina.
Hsu: Dilates peripheral blood vessels, lowers blood pressure; strong antibacterial properties.
DY: Engenders new tissue; nourishes the heart.
• With Mu dan pi to quicken the blood and dispel stasis, cool the blood, and eliminate deficiency heat. For indications such as:
– 1. Hematemesis, epistaxis, metrorrhagia, purpura, and also rubella and pruritis due to heat in the blood division.
– 2. Menstrual irregularities, dysmenorrhea, amenorrhea, dark purple menstrual blood with clots, and postpartum abdominal pain due to heat in the blood which causes blood stasis.
– 3. Continuous, low-grade fever due to Yin deficiency heat. In this case, if there are night sweats, use Di gu pi instead of Mu dan pi.
– 4. Hot, red, swollen, painful joints due to hot Bi or impediment.
• With San qi to quicken the blood, dispel stasis, nourish the heart, open the network vessels, stop pain, and settle palpitations. For indications such as chest Bi or impediment, i.e. cardiac problems with pain and severe palpitations. For these indications, wine mix-fried Dan shen should be used. This combination treats heart pain no matter what the cause. This action may be reinforced by adding Shi chang pu, Xie bai, Gua lou pi, Gui zhi, and Tan xiang.
• With Tan xiang to regulate and rectify the Qi and blood, move the Qi and blood, free the flow of the network vessels, and stop pain. For the following indications, wine mix-fried Dan shen should be used:
– 1. Chest Bi or impediment, heart diseases with severe cardiac pain due to Qi and blood stasis. If heart blood stasis is severe, add San qi, Hong hua, and Yan hu suo. If Qi stagnation is severe, add Chen xiang and Qing mu xiang. If there is phlegm-damp obstruction in the chest, Gua lou pi, Jie geng, and Zhi ke. If there is chest Yang deficiency, add Xie bai, Gui zhi, and Fu zi. If there is Qi deficiency, add Huang qi, Zhi gan cao, and Ren shen.
– 2. Stomach pain due to Qi and blood stasis.
Dan shen has “very interesting action” on coronary heart disease, circulatory system diseases, and hypercholesterolemia.
Dan shen only mildly nourishes blood. To reinforce its supplementing action, it should be prepared with pig or tortoise blood.
Dan shen is incompatible with vinegar or any other very sour or acrid food.
IBIS: Occasional hypersensitivity may lead to excessive bleeding or fever.
Weng Weiliang, et al: Clinical studies excerpted from Weng Weiliang, et al., Clinical Chinese materia medica, Henan Science & Technology Press, 1998, retrieved HERE:
• Viral myocarditis: Experiential formula Si Shen Yin which consisted of dan shen 12g, hai er shen 12g, nan sha shen 9g, ku shen 9g, zhi gan cao 3g, guang yu jin 9g, chao zao ren 9g, lian zi xin 2g was made into granules to treat viral myocarditis. Twice daily, 1 pack every time. 39 cases were treated, the courses of treatment ranged between 20 to 60 days, and the clinic symptoms improved to different extent.
• Acute myocardial infarction: Dan Shen Injection 10g~24g was added into 500ml 5% glucose or low molecular dextran for intravenous drip. Once daily, 7~14 days as a course of treatment. 388 cases of acute myocardial infarction were treated, the incidence rate of heart failure was 29.9%, the mortality rate within hospitalization was 27.2%, which were lower that those in the control group but without statistic significance. The mortality rate in males was 16.2% and was significantly lower than that of the control group. No difference in female group.
• Diabetes: Compound Dan Shen Injection 8~12ml was added into 500m 0.9% NaCl Injection for intravenous injection, once daily, for 28 to 43 days. 120 cases of diabetes were treat, 50 cases were markedly effective, 55 improved, 15 had no changes.
• Hepatocirrhosis: 20ml Compound Dan Shen Injection was added into 250ml low molecular dextran for intravenous drip, once daily, 30 days as a course of treatment. 43 cases of hepatocirrhosis were treated, 10 were markedly effective, 28 effective, and 5 ineffective..
• Chronic simple rhinitis: 2ml Compound Dan Shen Injection (each ml contains 2g dan shen and 2g jiang xiang) was mixed with 2ml physiological saline solution for nasal drip to treat chronic simple rhinitis. Three times daily, 2 drops each side every time. 4 weeks as a course of treatment. 38 cases were treated, 22 were cured, 10 markedly effective, 3 improved, and 3 ineffective.
WIKI: Results from animal and human studies support the use of Danshen for circulatory disorders to some extent because it is known to decrease the blood’s ability to clot in at least two ways. First, it limits the stickiness of blood platelets. It also decreases the production of fibrin, the threads of protein that trap blood cells to form clots. Both these effects help to improve blood circulation. In addition, chemicals in danshen may relax and widen blood vessels, especially those around the heart. In animal studies, chemicals in danshen may also have protected the inner linings of arteries from damage. Some other research suggests it may increase the force of heartbeats and slow the heart rate slightly.
• In animal studies, Danshen has appeared to interfere with the development of liver fibrosis — the formation of scar-like fibers in the liver. Because the nonfunctioning fibers crowd out active liver tissue, liver function decreases gradually as the amount of fibrous tissue increases. Having chronic hepatitis and habitually drinking large amounts of alcoholic beverages are the major causes of liver fibrosis, which could also result from exposure to chemicals or certain drugs. Danshen may also increase blood flow into the liver, so the length of time that potentially damaging substances stay in the liver may be reduced, also reducing the possible injury they may cause. Results from a few animal studies showed it may also protect kidney tissues from damage caused by diabetes. In China, danshen has also been studied for treating acute pancreatitis, a painful and possibly dangerous inflammation of the pancreas. [23]
Salvia miltiorrhiza inhibits alpha-glucosidase activity.[24]
• Danshen may stop the spread of several different cancer cell types by interrupting the cell division process[25] and also by causing cancer cells to undergo cell death (apoptosis).[15] In contrast, the cerebrovascular protective effect of Salvianolic acid has been found to be due to prevention of apoptosis.[9]
• For HIV, chemicals in Danshen may block the effectiveness of an enzyme, HIV-1 integrase, that the virus needs to replicate.[26]
• Salvia may stimulate dopamine release and has protective effects against free radical-induced cell toxicity.[27][28]
S. miltiorrhiza stimulates increased osteogenesis in vivo (bone cell growth).[29]
• Salvianolic acid B could possibly facilitate the repair of tubular epithelial structures and the regression of renal fibrosis in injured kidneys.[30]
• Danshen has been shown to potentiate the effects of the common anticoagulation drug warfarin, leading to gross anticoagulation and bleeding complications. Danshen should be avoided by those using warfarin.[31]

Dose: 6-15g (up to 60g when used alone or in treating vasculitis)

E Zhu – Zedoaria rhizome – Curcuma zedoaria, C. aromatica, or C. kwangsinensis

Nature: acrid, bitter, warm

Enters: Liver, Spleen

Actions: Strongly promotes blood and Qi circulation and dispels blood stasis; dissolves accumulations, eliminates food retention; relieves pain.

Indications:
• Blood stasis: amenorrhea with abdominal pain and masses, ovarian cysts, fibroids, epigastric masses.
• Food retention: fullness, constriction, distention, pain in the epigastrium, chest, and abdomen.
• Childhood nutritional impairment.
• Controls some cancers – particularly cervical (especially grade II and below).
• Stimulates motility of GI tract.
• Its powerful nature can damage the Qi (do not use for long periods).
• This is the strongest herb in the pharmacopeia to eliminate food retention.
• Much stronger than Ru xiang and Mo yao to move blood and relieve pain.
• Often combined with San leng. Liu says E zhu is stronger than San leng at moving blood, but weaker than San leng at moving Qi. Bensky/Gamble says just the opposite.
• Fry with vinegar to enhance its blood circulating properties and stop pain.
• Kamto: San leng + E zhu is a great combination for treating depression.
RW: Carminative (a type of turmeric).
Li: (Often with San leng) for blood stasis in difficult skin conditions.
PCBDP: Aromatic; stimulant; treats some tumors.
Hsu: Some antihistamine effects; promotes resorption of coagulated blood; inhibits cancer cell growth; stomachic.
HF: An important herb in anti-Gu therapy to move Qi (xing Qi) and break accumulation (po ji).
DY: Breaks the Qi and quickens the blood; treats the blood within the Qi; treats Qi stagnation which causes blood stagnation; tropism: liver, spleen, and Qi division.
• With San leng to strongly and effectively break both the Qi and blood, regulate and rectify the Qi and blood, stop pain, and reduce food accumulation. (Note that breaking the Qi and breaking the blood are both attacking methods that can damage the Zhen Qi if used inappropriately, too much, or for too long.) For indications such as:
– 1. Abdominal lump glomus, hepatomegaly, splenomegaly due to blood and/or Qi stasis. (E Leng Zhu Yu Tang)
– 2. Amenorrhea, dysmenorrhea, menstrual clots, and infertility due to blood stasis. (San Leng Wan) Both herbs should be vinegar mix-fried for these indications.
– 3. Abdominal pain due to food accumulation. (E Zhu Wan) Vinegar mix-fried E zhu should be used.

Dose: 3-9g

Hong Hua – Carthamus flower – Safflower – “Red Flower”

Nature: very acrid, warm

Enters: Heart, Liver

Actions: Promotes blood circulation, dispels blood stasis from the channels, opens the channels; alleviates pain; unblocks the menses.

Indications:
• Blood stasis: dysmenorrhea, amenorrhea, postpartum abdominal pain or dizziness, abdominal masses, lochioschesis, traumatic injury – wounds and pain, painful obstruction of the chest, non-suppurative sores, carbuncles.
• Heat and blood stasis: dark red skin eruptions, suppressed rashes, including measles.
• Beneficial in coronary artery disease. May also lower cholesterol.
• For Berger’s disease, combine with Ru xiang, Mo yao, Dang gui, Tao ren.
• For angina pectoris, often combined with Tao ren, Dan shen, Chuan xiong.
• Usually added near the end of cooking a decoction – should not be cooked long.
• Contraindicated in pregnancy.
• Bensky/Gamble: To harmonize the blood, use 0.9-1.5g.
Chen: Used successfully in one study to treat peptic ulcer.
DY: In a small dose (1-2g), it can slightly nourish blood. In a moderate dose (3-5g), it harmonizes the blood. At the usual dose (6-10g), it quickens the blood. At a high dose (10-15g), it breaks blood [stasis].
• Tends to dispel stasis in the upper part of the body and in the channels.
• With Tao ren: Hong hua is stronger than Tao ren at moving blood, while Tao ren is stronger at dispelling stasis. Together, they complement and reinforce each other to effectively quicken the blood, dispel stasis, engender blood, and stop pain. For such indications as:
-1. Cardiac and chest pain due to heart blood stasis. (Add San qi, Dan shen, Xie bai, and Gua lou pi.)
– 2. Amenorrhea, dysmenorrhea, menstrual irregularities, and dark menstrual blood with clots due to blood stasis. (Tao Hong Si Wu Tang)
– 3. Fixed, stabbing, and severe pain aggravated by pressure due to blood stasis. The combination appears in many formulas for these indications, based on the location and nature of the pain (Xue Fu Zhu Yu Tang, Tong Qiao Zhu Yu Tang, Fu Yuan Huo Xue Tang, Shen Tong Zhu Yu Tang, etc.).
– 4. Traumatic injuries with pain and swelling due to blood stasis. (Xiao Zhong Zhi Tong Tang)
MLT: Similar to, but stronger than Western Calendula.
PCBDP: Laxative, diuretic.
Hsu: Stimulates the uterus to contract rhythmically/tonically – particularly effective in pregnancy – fast, long lasting effect.
Dose:  3-10g (0.9-1.5 to harmonize blood) See comments from Dui Yao above.

Hu Zhang – Bushy Knotweed root and rhizome – Polygonum cuspidatum – “Tiger’s Cane”

Nature: bitter, cold

Enters: Liver, Gallbladder, Lung

Actions: Promotes blood circulation; relieves pain; eliminates toxicity; clears heat; drains dampness; resolves phlegm; stops coughing; slightly promotes bowel movement.

Indications:
• Especially indicated for a combination of phlegm, damp, heat, and blood stasis.
• Blood stasis: amenorrhea, traumatic injury, Bi syndrome.
• Damp-heat: jaundice, turbid vaginal discharge, painful urination.
• Heat-toxicity: burns, snake bites, skin infections, carbuncles. Often the fresh ground herb is applied topically.
• Lung phlegm-heat: cough.
• Heat accumulation: constipation (use 30g – discharges heat, toxicity).
• Guohui Liu: especially useful for hepatitis.
• Many constituents (resveratrol, piceatannol, polydatin, emodin) with medicinal properties elucidated through modern research:
– (from the scholarly folks at Herbal Vitality of Sedona) Anti-angiogenic (vitro), antibacterial against streptococci (vitro)/ vibrio (vivo), decreases histamine release (vitro), decreases COX-2 expression (vitro), anti-oxidant (vitro), antiviral – hepatitis B (vitro), anti-inflammatory (vivo), anti-allergenic (vivo), protects against burns (vivo), tyrosine kinase inhibitor, decreases oncogene function (vitro), neuroprotective (emodin / vivo), decreases leukopenia due to radiation (emodin / vivo), polydatin is cardioprotective (vitro) and decreases CAM expression (vivo), resveratrol has glucose regulating properties (vitro), inhibits cancer cell lines (vitro), decreases VEGF activity (vivo), decreases expression of NF-KappaB, COX-2, MMP9 (vivo), protects against bone loss (vivo), and is anti-inflammatory (vivo); piceatannol is hypolipidemic (vivo); stilbenes cause apoptosis of leukemic cells (vitro).
• Antiviral, antibacterial.
• Promotes leukocyte proliferation for leukopenia (particularly due to radiation or toxic chemicals).
• Contraindicated in pregnancy.

Dose: 9-30g

Ji Xue Teng – Millettia or Spatholobus root and vine

Nature: bitter, slightly sweet, warm

Enters: Liver, Heart, Spleen

Actions: Promotes blood circulation; mildly nourishes blood; relaxes the tendons; activates the collaterals, dispels stasis from the channels and collaterals; unblocks the menses.

Indications:
• Blood stasis: irregular menstruation, slow menstrual flow, dysmenorrhea, Bi syndrome.
• Blood stasis with blood deficiency: amenorrhea.
• Wind-dampness with blood deficiency or blood stasis: numb extremities, lumbar pain, knee pain, generalized joint soreness.
• Blood stasis or wind-stroke: weak extremities in the elderly, or paralysis and vertigo.
• For leukopenia from chemotherapy, radiation, aplastic anemia – combined with Dang gui, Bai shao, Shu di huang.
Hong teng – Sargentodoxa – (an herb that clears heat and eliminates toxicity) is used as this herb in many parts of China. It has none of Ji xue teng’s blood-nourishing properties or the ability to relax the tendons. Efforts should be taken to procure the correct herb if Ji xue teng’s unique properties are desired.
Hsu: Hypotensive.
Subhuti Dharmananda: May help antidote lead poisoning.
Millettia is the common name that has been selected to refer to the stems, obtained from several climbing legume shrubs containing a red resin, that are labeled as jixueteng in Chinese. The Chinese name describes the material as a stem (teng) with a sap having a color, which is reddish brown, reminiscent of dried chicken’s blood (ji = chicken; xue = blood). The main species used as sources of this herb are:
1. Spatholobus suberectus (most common species traded today and the official species in the Pharmacopoeia of the People’s Republic of China); see Figure 1; additionally Spatholobus harmandii and Spatholobus sinensis are used as substitutes.
2. Millettia dielsiana, Millettia nitida, Millettia speciosa, Millettia gentliana, Millettia reticulata, Millettia pachycarpa.
3. Mucuna birdwoodiana, Mucuna sempervirens, Mucuna castanea.
This group of plants represents a relatively recent addition to the Chinese Materia Medica, first recorded two centuries ago in the Bencao Gangmu Shiyi (Omissions from the Grand Materia Medica, 1765 A.D.), where it was said that it “activates blood, warms the waist and knees, and cures paralysis caused by wind.” This herb is not included in any of the commonly mentioned traditional herb formulas from the Qing Dynasty (1644–1911 A.D.).
Jixueteng did not have a strong reputation among traditional herbalists during the 20th century prior to the 1980’s. In Medicinal Plants of East and Southeast Asia (1), a compilation of information gathered during 1959–1961, the genera listed above are mentioned:
· Under the heading Mucuna it is stated that “Mucuna is scarcely worth mentioning medicinally.” The limitedinformation for this genus is that it “is a tonic.”
· Under the heading Millettia, it is stated that it “has few uses from the Malay Peninsula and Indonesia;” some mention of the leaves and root are made, but not of the stem; as to Chinese use, it is mentioned that Millettia dielsiana is “employed locally in Yunnan as anti-anemic; a new compound was isolated from the reddish bark; Millettia pachycarpa is used as a tonic and to induce the growth of red blood cells.”
· For Spatholobus, Chinese uses are not mentioned, though applications in Burma and Indonesia include: “ingestion of the sap as a treatment for faulty menstruation and uterine hemorrhage; an infusion of the stem is taken also to treat cough and fever.”
Jixueteng was deemed inconsequential enough that it was not included in the Synopsis of the Pharmacopoeia (2) prepared at the American College of Traditional Chinese Medicine in 1984, though the authors mentioned the herb in some sample prescriptions for recovering the hemopoietic system in their 1980 booklet Treatment of Toxic Side Effects Resulting From Radiation and Chemotherapy by Traditional Chinese Medicine (17). The herb is also absent from many of the illustrated Materia Medica guides that were compiled during the 1980’s. In the
book Aging and Blood Stasis (32), written by a physician who worked from the 1930’s to the 1980’s, jixueteng, commonly classified as an herb for promoting blood circulation and treating blood stasis, is not included in any of the prescriptions. The situation has changed dramatically in recent years: millettia has been elevated to one of the commonly used herbs of modern Chinese medicine.
TRADITIONAL ACTIONS AND INDICATIONS
The traditional actions of jixueteng mentioned in modern works, such as Chinese-English Manual of Common-Used Herbs of Traditional Chinese Medicine (3), are: “To enrich the blood and promote blood circulation, relax tendons and activate meridians.” Traditional indications are: “For blood deficiency and blood stasis syndrome manifesting as anemia, menalgia (painful menstruation), menoxenia (menstrual bleeding), or soreness, numbness, and immovability of extremities.” As another example, in Modern Study and Application of Materia Medica (43), its actions are: “To tonify the blood and activate its circulation, relieve rigidity of muscles and joints, and promote menstruation.” The indications are “Arthralgia due to wind and dampness, aching pain in the waist and knees, numbness of the extremities, malnutrition of the muscles and tendons, and irregular menstruation and amenorrhea due to deficiency of the blood.”
Depending on the source book consulted, jixueteng is found classified either as a blood nourishing herb, along with tang-kuei, peony, rehmannia, and ho-shou-wu, or as a blood vitalizing herb, along with salvia and red peony. In recent attempts to classify the blood vitalizing herbs into subgroups, Li Lianda (21) placed millettia along with tangkuei, moutan, salvia, raw rehmannia, and red peony as “mildly active herbs, nourishing the blood to promote circulation.”
C.S. Cheung (24) explained the close relationship of generating blood and vitalizing blood this way: The essence of fluid and grain is injected into the meridians and forms yingqi. It then circulates to the heart and transforms into blood. The blood flows to every part of the body and moistens and lubricates all tissues. When there is insufficiency of yingqi, the vaporization [dispersement] of qi is endangered. Thus, the blood does not flow smoothly, encouraging the formation of blood stasis and ecchymosis [congealed blood, outside the vessels]. New blood is unable to be generated when obstructed by stasis and ecchymosis. Consequently, therapeutic measures are taken to remove the obstruction and regenerate blood.
For this function, Cheung mentions the herbs tang-kuei, salvia, millettia, and turtle shell. Under millettia, he describes the functions as “tonifies and circulates blood, loosens ligaments, vitalizes the luo vessels, eliminates blood stasis and ecchymosis, and generates new blood and tissue.” The indications given are “blood deficiency diseases involving the meridians, draft wetness, numbness, cold pain.”
Qin Bowei (23), a famous herbalist of the 20th century, stated that: In harmonizing the blood, jixueteng is best at quickening the network vessels and freeing the channels. Cooked into paste, it is referred to as Jixueteng Jiao and is particularly strong. Yu Nanzhi [a famous herbalist] refers to this as a great supplementer of qi and blood, being most appropriate in geriatric and gynecological illnesses.
References to “activate meridians,” “vitalize the luo vessels,” and “free the channels” are translations of the Chinese term tongmai. Mai is the general term that means a vessel, channel, meridian, or a passageway, and the term is used in the modern medical sense of blood vessel. Tong means to be able to pass through or, as an activity, to make passable. Thus, tongmai indicates that use of the herb makes it possible for the qi and blood to flow through the meridians without obstruction. Where there is obstruction, one can experience pain, numbness, swelling, and stiffness. In general, the method of activating meridians is based on warming up the yangqi to promote vigorous movement.
The ability of millettia to supplement qi and blood, vitalize blood, alleviate cold pain, and free the channels brings to mind a traditional formula with similar properties: Huangqi Guizhi Wuwu Tang (Astragalus and Cinnamon Five Herb Combination) comprised of astragalus, peony, cinnamon, ginger, and jujube. Designed long before millettia was added to the Chinese Materia Medica, this formula is from the Jin Gui Yao Lue (ca. 220 A.D.). A modification of the formula was recommended by Wang Weilan (25) for treating soreness and weakness in the back and knees and numbness of the extremities in persons with qi and blood deficiency. To the traditional formula, he added tang-kuei, millettia, red peony, citrus, and chin-chiu (this last herb is often prescribed when there is a wind-damp syndrome in persons of deficiency constitution). He  particularly favored the combination of millettia with red peony in formulas for bi syndrome (arthralgia, numbness) to vitalize the blood, open the luo vessels, relax the ligaments, and relieve pain. In explaining bi syndrome, he stated that:
Deficiency of the normal qi is the basis of the internal factor and leads to the looseness of the cutaneous tissue [openness to external influence] and the lowering of the body’s resistance. If the external factor is the contraction of cold in winter, then the cold evil can take the opportunity to enter the weak and deficient body and to directly strike at the ligaments and bones, thus causing internal damage to the blood and the meridians, qi stagnation, blood stasis and ecchymosis, and limitation of movements….
According to this interpretation, herbs that enhance qi and blood, dispel the cold, and vitalize blood are of particular importance; hence, millettia is a key herb in treating bi syndrome in persons with deficiency syndrome.

RECENT APPLICATIONS OF MILLETTIA
It is the purported ability of millettia to aid the production of blood cells that has captured the attention of several Chinese researchers. A formula was developed for this purpose called Tang-kuei and Millettia Combination (Danggui Jixueteng Tang), recorded in the book Zhongyi Shanke Xue (Chinese Medicine for Blood Disorders) and relayed in Thousand Formulas and Thousand Herbs of Traditional Chinese Medicine (4):
Tang-kuei and Millettia Combination
Tang-kuei 15 g
Millettia 15 g
Rehmannia 15 g
Salvia 9 g
Peony 9 g
Longan 6 g
This formula follows the principle of vitalizing blood to generate new blood and nourishing blood to aid circulation of blood; it is indicated for “advanced stage of bone [marrow] injuries with qi and blood deficiency, or for the tumors with white blood cell or platelet reduction during chemotherapy or radiation therapy (4).” In modern practice, astragalus is often included in formulations of this type to treat the qi deficiency and aid in the generation of blood, even though millettia has been said to have the ability to generate qi.
A number of basic preparations of millettia have been described in recent literature. Millettia paste was mentioned in the Annals of Shunning Fu (40), where it was stated that: “When combined with carthamus, tangkuei, and oryza, and cooked into paste, jixueteng is a sacred herb for blood diseases.” Millettia Wine and Millettia, Shouwu, and Longan Wine are mentioned as treatments of wind diseases and blood deficiency syndrome: millettia, as a single herb, for bi syndrome (arthralgia and myalgia), and the three-ingredient wine for “lassitude of extremities,
dizziness, palpitation, insomnia, early greying of hair, and pallor due to deficiency of both qi and blood (41).”
Millettia Sugar Broth, in which jixueteng is decocted and combined with 40% its weight of sugar, and used for treating loss of blood and anemia, is mentioned in Chinese Medicinal Herbs (40). Millettia usage in food therapy has also been described (44, 45). Millettia is boiled with eggs (after the egg is hard boiled, the shell is removed, and the egg returned to the decoction for continued cooking); sometimes jujube is included. Then, the eggs are eaten and the decoction drunk as a treatment for anemia. A tablet made of jiexueteng extract as the sole ingredient, Jixueteng Qingao Pian, is produced by the Shanghai Native Medicine Works; it is described as a treatment for bi syndrome; amenorrhea or dysmenorrhea due to deficiency of blood and/or stagnation of blood; and increasing white blood cell count in cancer patients who suffer leukopenia due to chemotherapy or radiation (42). Jixueteng injection has also been prepared in China (37). In Dictionary of Chinese Medicine (40, 43), the simple decoction of 30 grams millettia given daily on a long term basis was reported helpful for leukopenia induced by radiation therapy. During the 1980’s and up to the present, several clinical trials were conducted involving treatment of leukopenia and thrombocytopenia in which millettia was included in the herbal formulas and results of the therapy were reported in Chinese medical journals.
REVIEW OF HERB THERAPIES TO COUNTERACT CHEMOTHERAPY-INDUCED LEUKOPENIA
In an extensive review article (Countering the side effects of modern medical therapies with Chinese herbs), the use of formulas that had been reported, according to the results of clinical trials, as successfully countering leukopenia was presented. The descriptions of formulas that contained millettia and the results claimed from giving them to patients are relayed again here, with slight editing of information from the previous article and a few additions.
The Astragalus-Jujube Combination (Qi Zao Granule) was applied to treating white blood cell suppression from various causes (5). The formula is comprised of 18 grams each of astragalus, jujube, millettia, and hoelen, concentrated into extract granules. According to the clinical report, patients with white blood cell counts below 3.5 were treated for 20–30 days with this mixture: 56% of the patients had their white cell counts increased by at least 4.0 above the initial value and 24% had the white cell counts increased at least 1.0 above the initial value; granulocytes similarly increased. The figures for the response of the control group were 25% and 5% respectively. The same formula was used in the treament of cor pulmonale (22), with lymphocyte transformation rate depressed by the treatment, indicating that the primary effect in leukopenic patients was to benefit white blood cell production.
An expanded version of that formula was clinically tested for cancer patients with impaired immune functions (6). The prescription, Shengxue Tang (Generate Blood Decoction), is made with 30 grams each of astragalus and millettia, and 10–15 grams each of hoelen, lycium fruit, pseudostellaria, ligustrum, and cuscuta (the latter four herbs replacing jujube in the Astragalus-Jujube Combination). According to the clinical report, 242 cancer patients, mostly having stomach or intestinal cancer, and being diagnosed as having spleen-qi deficiency, were administered this formula. After only a few days of treatment (each course of therapy was only 2–3 days), macrophage phagocytosis, lymphocyte transformation rates, E-rosette formation rates, and killing ability of natural killer cells of peripheral blood were significantly increased.
Although reversal of leukopenia was not a direct outcome measure for the study of Shengxue Tang, the prescription is similar to others that were demonstrated to have that outcome. For example, another version of this formula, labeled Fuzheng Zengxiao Fang, was reported to ameliorate leukopenia, as well as to significantly reduce the experience of fatigue and gastro-intestinal distress in cancer patients undergoing chemotherapy (7). The formula is comprised of astragalus, millettia, lycium fruit, ligustrum, pseudostellaria, atractylodes, asparagus, and carthamus (thus, hoelen and cuscuta in Shengxue Tang are replaced by atractylodes, asparagus, and carthamus).
In another study, patients completing treatment with chemotherapy and radiation therapy (mainly for lung and esophageal cancers) were then administered a modified version of Shiquan Dabu Tang (Ginseng and Tang-kuei Ten Combination), with the added herbs: millettia, polygonatum, lycium fruit, ho-shou-wu, cornus, lotus seed, and dioscorea. After 30 days administration of the herbs to 60 patients, it was reported (8) that there were statistically significant improvements in total white blood cells, natural killer-cell rate, and ratios of CD2, CD4, and CD8.

Another formula of similar nature was used in a study (9) on the side effects of cancer therapy in patients with many types of cancer. The formula is:
Huten Tang
astragalus 40 g
millettia 30 g
hoelen 30 g
hu-chang 30 g
cuscuta 20 g
lycium fruit 15 g
psoralea 15 g
tang-kuei 15 g
atractylodes 12 g
licorice 10 g
Hu-chang and millettia (both used to boost white blood cells) were deemed the main herbs in the formula. The herb therapy was initiated 3–5 days prior to starting chemotherapy and continued until one week after finishing chemotherapy. The effectiveness of the therapy was evaluated by considering a broad set of indicators, such as red and white blood cell levels, extent of gastro-intestinal reactions, avoiding loss of hair, and improving tumor shrinkage. According to the author, 39% of the patients had an excellent outcome, and 43% had a notably effective response,
while only 7% failed to respond at all. This prescription is an elaboration of one described for leukopenia due to radiotherapy (40), which is comprised of 30 grams each of hu-chang, millettia, and tang-kuei (all used for building blood), along with 9 grams of licorice.
A formula relying on similar key herbs and the same basic therapeutic principle was used for 60 cases of leukopenia (38), given astragalus, millettia, hu-chang, psoralea, gelatin, polygonatum, rubia, and jujube. It was reported that 52 of the patients had marked improvement in the lymphocyte counts, and that the average hemoglobin and platelet counts also increased.
The same basic principle of therapy was utilized in another trial (11) involving patients being treated mainly for tumors of the lung, breast, and stomach, with the following formulation:
Fuzheng Guben Fang
astragalus 40 g
ho-shou-wu 40 g
millettia 30 g
oldenlandia 30 g
pseudostellaria 30 g
gelatin 20 g
licorice 20 g
ligustrum 20 g
rehmannia 20 g
atractylodes 15 g
peony 15 g
tang-kuei 15 g
The formula was modified to address specific symptoms. The herbs were given along with chemotherapy, while a control group received Western drugs, vitamins, and berbamine (an herbal leukocyte raising alkaloid derived from sankezhen: Berberis soulieana) along with their chemotherapy. According to the report, the formula prevented the decline in leukocytes better than the control treatment, and the patients also had fewer other side effects, such as nausea and weariness.
In a review (12) of herbal treatments for granulocytopenia (a type of leukopenia), 28 recipes that were reported to be highly effective were analyzed. It was found that the most commonly used herb ingredients were astragalus (in 21 formulas) and jixueteng (in 20 formulas), followed by salvia (in 13 formulas), psoralea (in 12 formulas) and tangkuei (in 11 formulas). Other herbs that were used repeatedly but in fewer than 10 formulas each were ligustrum, jujube, lycium fruit, epimedium, licorice, and hu-chang. A tablet made primarily with the commonly used herbs,
including psoralea, epimedium, ligustrum, astragalus, jujube, tang-kuei, salvia, millettia, and hu-chang, and also containing placenta, cornus, and sanqi (13), was given to cancer patients who suffered leukopenia due to cancer chemotherapy as well as others suffering from leukopenia due to other causes (e.g., chronic hepatitis, drug poisoning, radiation, and unknown causes). According to the report, after a course of treatment of two weeks (15 tablets per day, each tablet 1.85 grams of herb material), leukopenia was completely reversed in 49% of patients and another
29% showed marked improvement in leukocyte counts.
In a mouse study of herbal effects on cyclophosphamide-induced leukopenia, a mixture of astragalus, hu-chang (hu zhang), and millettia (Huanghuji Mixture) was compared to the effect of hu-chang alone and with the effect of vitamin B4. According to the report (14), hu-chang had the greatest effect, with the Huanghuji mixture slightly less effective, and vitamin B4 having a relatively weak effect.
According to a review of cancer therapy approaches used in China (27), the herbal combination Dao Jing Tong #17, with main ingredients millettia, salvia, and curcuma, was reported to enhance the action of the anti-cancer drug camptothecin against leukemia and it protects against pulmonary fibrosis caused by radiation therapy (these effects were reported in mice studies). It was also reported that “Various preparations for raising the white cell count have been made with the following ingredients: Illicium verum (dahuixiang), sophora, and millettia. They have been used in hundreds of cases of radiation and chemotherapy induced agranulocytosis.” These three herbs are in the legume family (see: Legumes).
THROMBOCYTOPENIA
Millettia has been incorporated into several modern prescriptions for treating thrombocytopenia. For example, in a series of reports (10, 33), Fu Xian Tang, also called Sanyao Fang: a decoction made with 30 grams each of millettia and agrimony, and 9 grams of rumex (suanmogen), was given for treatment of thrombocytopenia (33). It was reported that 57 of 62 cases had their platelet count raised to over 100,000. This response occurred within one week for most patients. As another example, a decoction of 15–30 grams each of astragalus, millettia, and codonopsis, 10–30 grams each of tang-kuei and cnidium, 8–10 grams carthamus, and 10–30 grams each of red peony and leonurus, was given one dose per day to patients for an average of one month each (range: one week to two months). In all of the 18 cases of idiopathic thrombocytic purpura (ITP), the platelet count increased to greater than 100,000, but the effects were short-lasting in all but 5 cases (15).
In a study of 46 cases of ITP, patients were divided into two groups: those with blood stasis syndrome and those with spleen deficiency syndrome (26). For the former group, the general prescription given (which could be modified for individual cases) was comprised of millettia, red peony, rubia, tang-kuei, salvia, codonopsis, jujube, eclipta, and rehmannia (separately, a cup of tea made from notoginseng flowers was given). Of the 30 cases with the blood stasis type, the treatment was deemed markedly effective or effective in half the cases, and there was some improvement in all but three cases. The average course of therapy was 12 weeks.
A study of three treatments for ITP was conducted using either prednisone, coenzyme A, or a Chinese herb decoction (29) made with 20 grams each of astragalus and polygonatum plus 12 grams atractylodes to tonify qi, 15 grams each of millettia and tang-kuei to nourish and vitalize blood; 12 grams each of red peony and moutan to vitalize blood and cool blood heat; and 10 grams of carthamus to vitalize blood and resolve stasis. Treatments were administered for 4–8 weeks. According to the study report, prednisone had the strongest effect (82% rate of improvement), Chinese herbs had a good effect (65% rate of improvement), and coenzyme A had only a slight effect (35% improvement, but none markedly effective).
Patients with advanced gastric adenoma undergoing chemotherapy were treated (16) with Shengxue Tang, a decoction containing astragalus, millettia, ligustrum, cuscuta, lycium, pseudostellaria, atractylodes, and hoelen; it was reported that six weeks administration along with the chemotherapy resulted in increased platelet counts.
Patients with acute leukemia often suffer from thrombocytopenia, since the cancerous stem cells that produce leukocytes crowd out the cells that produce platelets. In a study of combined Chinese medical and Western medical treament of acute leukemia (49), 30 patients received standard chemotherapy alone (as a control) or in combination with a decoction made from two types of jixueteng (30 grams each of Spatholobus and Mucuna) and 15 grams of another member of the legume family that has similar actions, moghania (yitiaogen), plus a complex formula
containing cynanchum, frankincense, phragmites, hoelen, cissus, pueraria, rehmannia, polygonatum, ligustrum, and oldenlandia (each herb in dosages of 10–30 grams). According to the report, in addition to improving the level of platelets and red blood cells, the herbs contributed to a higher rate of remission than in the control group (83% vs. 63%) and a longer average duration of remission (390 days vs. 268 days).
DOSAGE AND COMBINING
The dosage recommendations for millettia vary among the Materia Medica descriptions. The frequently cited dosage ranges are 9–15 grams per day or 15–30 grams per day, but some sources mention up to 60 grams per day. In one book describing individual species (45), for Millettia nitida, a therapy using 60–120 grams per day was mentioned for anemia. Among the clinical reports reviewed here for which dosage was mentioned, 30 grams per day seems to be the standard amount used, though some formulas included only 15–18 grams. Millettia is frequently incorporated into prescriptions of 8 or more ingredients, but in four of the clinical reports mentioned above, it was used in small formulas with only 2–3 other herbs. Most commonly, millettia was combined with astragalus, lycium fruit, ligustrum, rehmannia, and tang-kuei in formulas for generating blood cells.
TOXICITY, ADVERSE EFFECTS, AND CONTRA-INDICATIONS
No reports of toxicity or adverse reaction to millettia have appeared in the Chinese literature available to ITM. In one report (37) on the safety of jixueteng injection (with Spatholobus suberectus specified as the source material), it was stated that its tolerance dose in mice was 200 times the therapeutic dose and that the LD50 in mice was over 100 g/kg, a huge amount. No irritation was induced by injecting the drug into different sites in rabbits. It did not cause allergic reaction in guinea pigs. If injected into mice at high dosage for several days after initiation of
pregnancy, it reduced the pregnancy rate; this effect was not observed in rats, however. High doses of millettia (15– 30 grams/day or more), such as used in correcting leukopenia, should not be used during pregnancy; in general, Chinese literature recommends avoiding blood-vitalizing herbs during pregnancy, with certain limited exceptions.
ACTIVE CONSTITUENTS
At this time, it is not clear which active constituents of jixueteng are responsible for the claimed effects of the herb in complex formulas, though it appears likely that the flavonoids are the dominant constituent of interest. There is a deficiency in information about the constituents and pharmacology in the literature that may reflect the fact that there are so many different source species involved. The Leguminoceae, family to which all the jixueteng species belong, provides four basic types of active constituents:
1. Flavonoids, which are the dominant group of active constituents for this plant family—found in most of the species in significant quantities—such as those from soybeans (e.g., genistein and diadzein) that have become well-known (see: Flavonoids for health; Soybeans for health). Psoralea, which is used with some frequency in the formulas for treating leukopenia, is a legume that is rich in flavonoids.
2. Alkaloids, such as oxymatrine and matrine found in sophora root, which also have the effect of protecting bone marrow functions (see: Sophora);
3. Saponins, including triterpenes, that are reputed to promote blood circulation, improve oxygen utilization, and protect against adverse influences (adaptogenic effect); and
4. Polysaccharides, such as those contained in astragalus, that are reported to counteract the bone marrow suppression induced by chemotherapy and to enhance macrophage functions (see: The physiological responses to immunologically-active polysaccharides);
Thus far, there have been no reports of medicinally active polysaccharides or alkaloids in jixueteng. Several flavonoid compounds have been identified for Millettia pachycarpa (18) and for Millettia reticulata (19). These are polymethoxyflavones, isoflavones, and flavonoid alcohols. Spatholobus suberectus, the most commonly used source of jixueteng in China today, was analyzed to reveal the following constituents (34, 40):
· Isoflavones similar to genistein (these are found also in pueraria flower and root, sophora tops, licorice root, wisteria, and soy bean): formononetin, ononin, afromosin, diadzein
· Chalcones (a group of flavonoids, found also in licorice root and sophora tops): isoliquiritigenin, tetrahydroxychalcone, licochalcone
· Coumestans (a group of flavones, found also in sophora tops, better known in alfalfa): medicagol
· Condensed flavonoids (also known as tannins and found in many herbs, notably green tea): epicatechin
· Other flavonoids: pruetin, cajinin, methoxyhydroflavonol
· Triterpenes: friedelan, taraxerone
· Sterols: beta-sitosterol, daucosterol, methoxycoumesterol, camphesterol, stigmasterol
· Phenolic organic acids: protocatechuic acid
Flavonoid compounds similar to those in Spatholobus have been found in other herbs that are reputed to have blood-vitalizing activity, such as dragon’s blood (Daemonorops draco: xuejie), sappan (Caesalpinia sappan; sumu) and dalbergia (Dalbergia odifera: jiangxiang); the latter two herbs are in the same plant family as millettia. Like the jixueteng vines, these other herbs have red resins; in fact, sappan was long known in Europe as brasil wood, which means “red dye” wood (the country of Brazil, where this plant was found growing, is named after it). The millettia flavonoids have platelet aggregation inhibiting effects and coronary dilating activity that helps explain their use in treating cardiovascular diseases (19). While many flavonoids are colorless, there are some that are pigments, such as afromosin in Spatholobus and brasilin in sappan. It is possible that the traditional Chinese focus on red colored herbs—originally selected because of the ancient concept that these were affiliated with blood circulation—has resulted in use of a group of herbs with highly effective blood-vitalizing flavonoids, some of which are red pigments.
NON-LEGUME SUBSTITUTES FOR JIXUETENG
A study of market materials used for jixueteng reveals that the following are also used (30, 31): Kadsura interior, Kadsura heteroclita, and Schizandra propinqua of the Schizandra Family (formerly included in the Magnolia family) and Sargentodoxa cuneata (of the Lardizabalaceae). Kadsura species are widely used in Chinese medicine; for example, kadsura bark (zijingpi) is said to invigorate blood circulation, disperse swelling, remove toxin, clean blood, regulate menstruation, and promote urination; kadsura rhizome (haifengteng) is said to remove wind and
dampness and promote the flow of meridians; and kadsura root (hongmuxiang; meaning fragrant red wood) is reported to move qi, invigorate blood, and control pain. These are properties attributed to jixueteng as well. Schizandra, a close relative, is usually used as a source of medicinal fruits, but it is the stem that is used for jixueteng. Sargentodoxa cuneata is known as hongteng (red stem) or as xueteng (blood stem) and is said to remove toxins and furuncles, invigorate blood circulation, promote the flow of channels, dispel wind, and kill intestinal parasites. Like the legumes that give rise to jixueteng, these plants have a red color and are reputed to promote circulation of blood. The active constituents have not been analyzed.
MECHANISM OF ACTION ON HEMOPOIETIC SYSTEM
In a recent study (20) of treatment of aplastic anemia, two formulas with jixueteng (one for invigorating yang, one for nourishing yin) were evaluated (dosages are in grams per day):
Jixueteng Zhengyang Tang
Millettia 100
Astragalus 60
Eclipta 30
Ligustrum 30
Ho-shou-wu 24
Cuscuta 18
Epimedium 18
Psoralea 12
Tang-kuei 12
Fenugreek 6
Placenta 6
Ginseng 3
Jixueteng Yijing Tang
Ligustrum 100
Eclipta 100
Rehmannia 90
Millettia 30
Ho-shou-wu 30
Astragalus 30
Salvia 24
Cuscuta 12
Gelatin 9
Lycium 9
Psoralea 6
Tang-kuei 6
The formulas were administered according to the primary diagnosis of either dominant yang deficiency or dominant yin deficiency. In certain circumstances, additional herbs and/or hormone therapy would be used as deemed necessary. Red blood cells, white blood cells, and platelets all increased significantly after patients received the herb treatment for several months (up to 2 years for this study). Bone marrow biopsies were used to evaluate the condition of the bone marrow before treatment (in 106 patients) and then after treatment in 45 patients who had good results based on their blood picture. According to the authors:
Before treatment, there were nucleated cells in 84% (89/106) among the cases with low hemopoietic tissue in the bone marrow, which had been replaced by fatty tissue. Re-examination of 45 cases after treatment showed hyperactive proliferation of bone marrow in 40 cases (89%), the lipid cells decreased, the percentage of granulocytic, erythroblastic, and megakaryotic series increased significantly, and the islands of erythroblastic series could easily be seen. The marrow vascular network was significantly reduced before treatment, even to the extent that no small vessel or capillary was found in sections from 22/106 cases (21%), and expanded and broken sinuses were found. After treatment, the number of vessels significantly increased and the morphology of the sinuses and capillaries became normal with intact wall structure. The reticulofibrosis (RF) of marrow increased after treatment and most of them were fine in appearance, distributed scantily in tissues. No cases showed RF of high degree [diffuse fibroreticulation accompanied with either scattered coarse fibers or local collagen fibrosis]….Study of the bone marrow matrix showed that the increase of vascular network, restoration of vascular structure, and proliferation of RF may be due to the more active new vessels and increased secretion of RF from adventitial reticulocytes to construct the matrix skeleton.
Although aplastic anemia differs from bone marrow suppression via chemotherapy or radiation, it is possible that improved microcirculation in the marrow vascular network could also explain some of the effects of millettia on the cancer therapy induced bone marrow suppression. In the cancer cases, the physical damage to the bone marrow is less than in aplastic anemia (at least, initially), but the impairment of stem cell activity might be accompanied by reduced microcirculation. Along these lines, it is of interest to note that another herb, hu-chang, frequently used with millettia in the formulas, has been classified as a blood vitalizing herb in several Chinese texts (sometimes, it is classified among the heat and toxin clearing herbs). In the Bencao Gangmu Shiyi where millettia was first recorded, it is commented that (40): “the decoction of hu-chang is effective for diseases of the bone joints and blood stasis.” It is possible that these two herbs are useful in the complex prescriptions for bone marrow disorders because of their contribution to bone marrow microcirculation. When accompanied by other herbs, such as those that contain
polysaccharides that may stimulate the bone marrow cells (e.g., astragalus, lycium, epimedium), the bone marrow may be able to function optimally within the limits imposed by the potent activity of the anticancer drugs or repeated radiation exposure.
In a study of mechanism of action of herbs on the bone marrow (28), researchers administered herbs to mice with cyclophosphamide-induced marrow suppression in three combinations:
1. A blood vitalizing combination comprised of 15 grams each millettia and salvia.
2. A kidney tonifying combination comprised of 30 grams each rehmannia and ho-shou-wu, plus 15 grams each of ligustrum, psoralea, and cistanche.
3. A combined therapy group with all seven of the above herbs.
According to the study analysis, the kidney tonification herbs (#2 above) enhanced the growth of marrow progenitors for granulocyte-macrophages (thus benefited leukocytes), while the blood-vitalizing group promoted the erythroid progenitors (thus increased red blood cells) and improved marrow stroma function (which benefits the granulocyte-macrophages). The combined therapy produced greater increases in each of the bone-marrow cell-lines than the component parts. The combination kidney-tonifying and blood-vitalizing therapy was given to 50 patients suffering from aplastic anemia (most patients also received stanazol); it was reported that 41 of them (82%) responded well, an improvement compared to the 57% of patients responding well to stanazol alone. Among 9 patients who received only the herbs, 5 had remission and 2 showed marked improvement.
Proposed mechanisms by which the bone marrow was restored by the herbal treatments included removal of sialic acid from cell membranes resulting in proliferation signaling, increase in cytokines that stimulate the stem cells, and restoration of superoxide dysmutase function. Electron microscope studies indicated that the blood-vitalizing herbs and the combined kidney-tonic and blood-vitalizing therapy were better than the kidney-tonifying therapy alone at recovering the micro-environment [capillary bed] of the bone marrow.
OTHER USES
In recent practice, jixueteng appears in several formulas reported in Chinese clinical trials for treating cardiovascular diseases, liver fibrosis, rheumatoid arthritis, sciatica, and skin diseases. However, the formulas are quite large, and several of the herbs contained in them are known to have the desired effects, so the role of millettia in these treatments is unclear.
As an example of the applications to treat skin ailments, following are two prescriptions with millettia from a literature review related in the book Treatment of Psoriasis with Traditional Chinese Medicine (35):
· Jinyin Huzhang Tang: 15 grams each of lonicera, hu-chang, salvia, millettia; 12 grams each of raw rehmannia, red peony, sophora flower, 9 grams isatis leaf
· Buxue Qufeng Tang: 30 grams each of astragalus, millettia, and polygonum stem; 15 grams each of raw rehmannia, and dictamnus; 12 grams each of codonopsis, tang-kuei, trichosanthes, and isatis leaf; 9 grams clematis; and 5 grams each of angelica, siler, and citrus.
Following is a formula that was reported useful for treating vitiligo in a clinical trial involving 30 cases (36):
· Huoxue Qufeng Tang: salvia, cnidium, millettia, tang-kuei, moutan, tribulus, schizonepeta, saussurea, magnetite (proportions not given).
The next formula was prescribed for chronic skin ulcers (39):
· Guizhi Tang Jiajian: cinnamon, peony, ginger, jujube, licorice, millettia, smilax, coix, tang-kuei, atractylodes, cyathula (proportions not given); it was reported that 41 of 48 patients suffering from skin ulcers due to persisting wound infections, burns, or varicose veins were cured.
In all of these treatments for skin ailments, millettia is combined with tang-kuei or salvia or both. These herbs are used to nourish blood and vitalize blood circulation.
As examples of using millettia to treat bi syndromes, a review of formulas in the book Bi Syndromes (46) provides the following modern modifications of traditional formulas (name of traditional formula given, followed by ingredients of modified version):
· Sanbi Wan: tu-huo, chin-chiu, clematis, stephania, chaenomeles, trachelospermum, eucommia, astragalus, cyathula, millettia, loranthus, tang-kuei, siler, cinnamon, and baked licorice. This is recommended for early stage arthritis, involving influence of wind, cold, and dampness (the three inducers of bi, sanbi).
· Fangfeng Tang: siler, ma-huang, tang-kuei, chin-chiu, pueraria, chiang-huo, schizonepeta, millettia, trachelospermum. This is indicated for “wandering bi,” in which the painful sensation migrates, rather than being always in a fixed location.
· Tao Hong Siwu Tang: astragalus, tang-kuei, codonopsis, cnidium, salvia, rehmannia, persica, carthamus, millettia, earthworm. This is used for skin bi, such as scleroderma, in persons with qi deficiency and blood stagnation syndrome.
· Shiquan Dabu Tang: ginseng, astragalus, rehmannia, tang-kuei, cinnamon, salvia, hoelen, millettia, baked licorice. This is used for blood vessel bi, such as arteritis, in persons with qi and blood deficiency syndrome.
· Shentong Zhuyu Tang: persica, carthamus, frankincense, myrrh, tang-kuei, cnidium, millettia, cyathula,liquidambar, chiang-huo. This is used for tendon bi, such as contracting pain in the limbs, in persons with blood stagnation syndrome.
· Wang Qiuzhou Tang: morus twig, kadsura, millettia, siegesbeckia, cinnamon, cnidium, peony, red peony, myrrh, frankincense; this is used for tennis elbow.
In addition, a patent remedy developed during the 1980’s, Yao Tong Ling (Anti-Lumbago Tablets, different than the one commonly marketed in the U.S.) is mentioned. It is comprised of tu-huo, chiang-huo, chin-chiu, kadsura, millettia, carthamus, tang-kuei, cnidium, asarum, cinnamon, eucommia, and rehmannia. Millettia has been included in other recent patent products, such as Duzhong Hugu Wan for chronic bi syndrome due to liver and kidney deficiency, and Mugua Wan for limb numbness and weakness (42, 48).
In all of these formulas for bi syndromes, millettia is accompanied by some of the ingredients of Siwu Tang, Tang-kuei Four Combination.
To treat multiple sclerosis, which involves limb numbness and paralysis, Chinese physicians have recommended formulas that include millettia (47). As examples:
· For deficiency of qi and weakness of the kidney: astragalus, morinda, cibotium, ophiopogon, cuscuta, pueraria, chaenomeles, achyranthes, tortoise shell, and millettia.
· For deficiency of kidney and liver, with phlegm-obstruction of the channels: tang-kuei, curcuma, rehmannia, hoelen, acorus, silkworm, ho-shou-wu, salvia, chaenomeles, peony, cnidium, millettia, and zizyphus.
In these formulas, millettia is combined with chaenomeles to treat stiffness of the extremities.
It can be seen, from the limited presentation of modern uses of millettia, that this herb has rapidly moved from obscurity to prominence in the practice of herbal medicine. No doubt, the increasing reliance on millettia will lead to further analysis of its constituents, pharmacology, and clinical application.
Dose: 9-15 (to 30g in severe cases)

 

Ji Xue Teng Jiao:
• This is Ji xue teng made into an enriched syrup by concentrating it and adding malt sugar syrup and extracts of Hong hua, Niu xi, Xu duan, and black beans.
• Slightly sweet, astringent, aromatic, warm.
• Similar effect to Ji xue teng, but stronger at nourishing blood.
• Dissolve it into a strained decoction.
Dose: 4.5-9g

Jiang Huang – Turmeric rhizome – Curcuma longa – “Ginger Yellow”

Nature: acrid, bitter, warm

Enters: Liver, Spleen, Stomach

Actions: Strongly promotes blood circulation; dispels blood stasis from the channels and collaterals; relieves pain; unblocks menstruation; disperses wind-cold; promotes Qi circulation.

Indications:
• Blood stasis: pain in the shoulder, chest, hypochondria, abdomen, and amenorrhea, dysmenorrhea. Especially effective for shoulder pain.
• Wind-cold-dampness: Bi syndrome, especially in shoulders, limbs.
• Blood stasis due to cold from deficiency.
• Topical: stops bleeding and pain.
• Can be made into an ointment with oil.
• Cholagogue.
• Stimulates the uterus.
• Lowers blood pressure.
• Curcuminoids, thought to be the primary active components (with curcumin being the most researched), are notoriously poorly absorbed. In Ayurveda, turmeric is often routinely combined with pippali (Bi Bo) and/or black pepper (Hu Jiao), to help its absorption. Interesting, a number of classic martial arts hit formulas (die da jiao) include the combination of Jiang Huang and Bi Bo. It’s now known that Bi Bo and Hu Jiao contain piperine, which enhances absorption of other compounds (and is used commercially as an absorption enhancer with a variety of nutritional supplements).
• One study showed piperine (the active pungent compound in black pepper – hu jiao – and pippali – bi bo) can dramatically increase the absorption of curcumin (perhaps as much as 2000%). [Planta Med. 1998 May;64(4):353-6. Influence of piperine on the pharmacokinetics of curcumin in animals and human volunteers.]
MLT: Increases bile flow, reduces liver enzymes SGOT and SGPT, prevents and dissolves gall stones.
• Anti-inflammatory, analgesic for sports injury, musculoskeletal trauma, inflammatory bowel disease, arthritis, rheumatoid arthritis.
BII: Contains curcumin – a powerful and safe anti-inflammatory; protective against cancer development.
• Possible uses in: atherosclerosis, cancer, gallbladder disease (curcumin increases bile acid output over 100%, and greatly increases the solubility of bile – may prevent and treat gall stones), rheumatoid arthritis, general inflammation.
Yoga: Haridra: K-; P, V+ (in excess)
• Stimulant, carminative, alterative, vulnerary, antibiotic while improving digestive flora.
• Gives the energy of the Divine Mother and grants prosperity.
• Cleanses the chakras, purifies the channels of the subtle-body.
• Helps stretch the ligaments, good for the practice of hatha yoga.
• Promotes proper metabolism.
• Topical: sprains, strains, bruises, itching.
Hsu: Increases the detoxifying abilities of liver.
• Stimulates the uterus to contract (paroxysmally).
• The ethanol extract is hypotensive.
CHA: (Karen S. Vaughan, 8-30-2001) Fungal infections of the feet: soaking the feet in a turmeric footbath is part of Ayurveda and is also done in traditional Hawaiian medicine.
Weil: Knee arthritis: This research, from Italy, was a three-month trial involving 50 patients diagnosed by x-ray with osteoarthritis of the knee. The Italian team was investigating the effect on arthritis symptoms of a special formulation of turmeric designed to improve its absorption by the body. Half the participating patients took the turmeric formulation in addition to standard medical treatment; those in the second group continued following their physicians’ recommendations.
After 90 days, the researchers found a 58 percent decrease in overall reported pain and stiffness as well as an improvement in physical functioning among the turmeric group compared to the controls. These changes were documented with a standard medical scoring method used to assess symptoms of knee and hip osteoarthritis. In addition, another scoring method showed a 300 percent improvement in the emotional well being of the turmeric patients compared with the others. And blood tests showed a 16-fold decline in C-reactive protein, a marker for inflammation. Patients in the turmeric group were able to reduce their use of non-steroidal anti-inflammatory drugs by 63 percent, compared to the other group.
Results of this study are very good news for the millions of people worldwide who suffer from osteoarthritis and haven’t been adequately helped by available treatments. The dose of the turmeric formulation used in the study was one gram per day. It is now commercially available in the United States and Europe.
Turmeric may also be useful for prevention of symptoms of rheumatoid arthritis, but this evidence comes from animal studies, not human trials.
Research also suggests that turmeric may prevent changes that lead to Alzheimer’s disease, and animal studies have shown that turmeric may be effective in the prevention or treatment of colon, breast and prostate cancers.

Dose: 3-9g

On Curcumin/Curcuminoids from Examine.com:
Curcumin is the yellow pigment associated with the curry spice, Turmeric, and to a lesser extent Ginger. It is a small molecule that is the prototypical ‘curcuminoid’, and has effects similar to other polyphenols but unique in a way as it is a different class of polyphenol (relative to the other classes of ‘flavonoid’, ‘stilbene’, etc.)

It exerts potent anti-inflammatory effects, and these anti-inflammatory effects seem to be quite protective against some form of cancer progression. However, curcumin has additional anti-cancer effects that are independent of its anti-inflammatory effects and thus is a heavily researched molecule for both cancer prevention and treatment.

Other areas of interest as it pertains to curcumin are alleviating cognitive decline associated with aging, being heart healthy by both electrical means and reducing lipid and plaque levels in arteries, and both reducing the risk of diabetes and being a good treatment for the side-effects associated with diabetes.

It has a poor oral bioavailability (a low percentage of what you consume is absorbed) and thus should be enhanced with other agents such as black pepper extract, called piperine. This is unless you want the curcumin in your colon (as it is a colon anti-inflammatory and can help with digestion), in which case you wouldn’t pair it with an enhancement.

Doses up to 8g curcuminoids in humans have been shown to not be associated with much adverse effects at all, and in vitro tests suggest curcumin has quite a large safety threshold.

A good general intake of curcumin, as a supplement, would be 500mg of curcuminoids that is enhanced in some manner. 500mg of curcumin with 20mg piperine, or 500mg of curcumin microsomes or curcumin phosphatidylcholine.

For any effects on colon and intestinal tissue (colon cancer prevention, reducing inflammation associated with Crohn’s, etc.) it would be good to use a dose of 2-4g curcumin or turmeric without any enhancement.

Benefits have been seen with as little as 100-200mg turmeric sprinkled on curry, so even if you don’t supplement it would be prudent to use some turmeric in daily life.

1.1. Sources

Curcumin (Diferuloylmethane) is the main active ingredient of the spice Turmeric (also known as Curcuma Longa or JiangHuang), which consists of Curcumin as well as thee other curcuminoids (Demethoxycurcumin , Bisdemethoxycurcumin, and Cyclocurcumin)[1][2] in which curcumin can consist of up to 80% of curcuminoids by weight, dependent on location of growth.[3] Both curcumin and Ginger belong to the family of Zingiberaceae known as the ‘Ginger Family’.

Curcuminoids appear in the entire Curcumin genus, although most commonly in Longa. Curcumoinds exist in:

Curcuma Longa (Turmeric, or JiangHuang) at around 22.21-40.36mg/g in the rhizomes and 1.94mg/g in the tuberous roots
Curcuma Phaeocaulis at 0.098mg/g in the rhizomes
Ginger
Shampoo ginger (Zingiber zerumbet L)

Other names for curcumin can be NCB-02 (a standardized mixture of curcuminoids), E100 (code used for food coloring), MERIVA (curcumin bound to soy lecithin, or phosphatidylcholine) and THERACURMIN (curcumin microsomes).

Commercially available extracts of ‘curcumin’ may not be wholly curcumin, but a blend consisting of 77% curcumin (17% demethoxycurcumin, 3% bisdemethoxycurcumin, last 3% not classified but assumed to possess a cyclocurcumin content).[11]

1.2. Structure and Properties

The structure of curcumin, officially known as diferuloylmethane, is two ferulic acid moeities bound together with an additional carbon to abridge the carboxyl groups. It can exist in a enol form (pictured below) or a keto form, which is molecularily symmetrical with two ketone groups on the backbone.

Curcumin is the compound in Turmeric which exert the characteristic bright, yellow color of Turmeric. Due to its intense coloration, it is sometimes used as a food additive with the code of E100.[12][8]

Curcumin is lipophilic and highly insoluble in water, and is acid-stable when measured around the pH of the stomach.[13]

2. Pharmacology

2.1. Absorption

Due to the poor intestinal absorption, however, curcumin is effective in reaching colonic tissue. An oral dose of 3.6g curcumin (which has been shown to increase plasma levels to 11.1+/-0.6nmol/L[14]) is able to increase the levels of curcumin in colorectal tissue to 7.7+/-1.8nmol/g (normal) and 12.7+/-5.7umol/g (malignant).[14]

2.2. Systemic

Curcumin, due to its lipophilicity, is transported in the blood via transports; most likely binding to Human Serum Albumin.[15]

Without aiding absorption, an oral dose of 500mg/kg bodyweight in rats results in peak plasma levels of 1.8ng/mL.[16]

When investigating humans oral dosages of 2, 4, and 8g curcumin daily for 3 months results in circulating levels of 0.51+/-0.11, 0.63+/-0.06, and 1.77+/-1.87uM; respectively. These Cmax values were attained around 1-2 hours post-administration and then rapidly declined.[17] Another human study found that 3.6g of curcumin resulted in levels of 11.1+/-0.6nmol/L an hour after consumption, with the lower dose tested (0.45g) not able to influence serum levels of curcumin;[14] this dose is about 1/45th the circulating amount of the 4g curcumin dosage in the previous study, and the reason for discrepancy is unclear.[17][14][18] Higher dosages induce a Cmax of 2.30+/-0.26 ?g/mL (10g) and 1.73+/-0.19 ?g/mL (12g); the reason for the drop in Cmax is unknown, but hypothesized to be due to saturation of the transporters.[19]

Increasing the oral dose to 10g induces an AUC of 35.33+/-3.78 ?g/mL, and a 12g dose induces an AUC of 26.57+/-2.97 ?g/mL.[19]

2.3. Bioavailability

The efficiency of an oral dose in increasing plasma levels of curcumin (bioavailability) is poor;[20] due to this, methods are being investigated to increase bioavailability. One clinical toxicology study in humans looking at oral curcumin found that doses below 8,000mg didn’t influence serum levels significantly, but only doses of 10g or 12g[21] (although some studies do note serum spikes at 4g).[17]

Pairing Curcumin with Piperine, a black pepper extract that is also an inhibitor of glucuronidation enzymes in the intestines and liver, is able to increase bioavailability 20-fold (2000% of baseline values) when 20mg piperine is paired with 2g curcumin.[22]

Complexing curcumin with phospholipids (a phosphatidylcholine-curcumin complex known as Meriva) can increase its incorporation into lipophilic membranes, increasing Cmax and AUC five-fold in rats[23] and making 450mg Meriva as effective as 4g curcumin in humans (unpublished trial).[18] Other trials suggest a factor of 29-fold higher absorption in humans, although said enhanced absorption favors demethoxycurcumin rather than curcumin.[24]

Beyond Piperine and Phospholipids, nanoparticle emulsions show promise. THEACURCUMIN emulsion (nanoparticles) possesses a 40-fold higher AUC (Area-under-Curve) when compared to basic curcumin power in rats, and a 27-fold higher AUC in humans.[10] although another study found merely a 10-fold increase in AUC and a 40-fold increase in Cmax in rodents.[25] This increased bioavailability is, in part, due to increased water-solubility.[26] Usage of nanoparticles can be used up to 210mg without any apparent saturation in absorption, and increase to Cmax to 275+/-67ng/mL, an AUC of 3,649+/-430 ng/ml/h, and a half-life of 13+/-3.3 hours.[26]

For any systemic purpose, it would be wise to increase curcumin bioavailability; either by taking it with a meal and piperine (Black Pepper) or one of the enhanced delivery systems. If using curcumin for any effects on the colon, poor bioavailability is desirable (if not absorbed, it heads to the colon) and no measures for bioavailability enhancement should be made

2.4. Metabolism

The major metabolites of curcumin in humans are curcumin sulfate (via sulfation enzymes of P450) and curcumin glucuronide (via glucuronidation by P450).[16][14][19]

In the bile, tetrahydrocurcumin and hexahydrocurcumin have been noted in rats, and to a lesser degree dihydroferulic acid and ferulic acid.[27]

2.5. Excretion and Clearance

One study using an intravenous dose of curcumin at 40mg/kg bodyweight in rats noted that the dose of curcumin was essentially cleared from plasma after one hour.[16]

3. Longevity and Life Extension

3.1. Autophagy

Autophagy is a Longevity associated process involving selective destruction of damaged cellular organelles, sometimes described as cellular housekeeping or maintenance;[28][29] autophagy appears to activated by many polyphenols[30] including curcumin, Resveratrol, silybin (from Milk Thistle), Quercetin, and catechin (common, but usually known to be a component of the four Green Tea Catechins).

Curcumin (and the metabolite tetrahydrocurcumin [31]) appear to induce autophagy via Akt/mTOR/p70S6K and ERK1/2 signalling pathways (inhibition and activation, respectively[32]) and so far has been detected in glioma,[32] uterine,[33] oral cancer,[34] and leukemic cells.[31] In drosophilia, flies with mutations in the osr-1, sek-1, mek-1, skn-1, unc-43, sir-2.1, or age-1 genes fail to have life extension from curcumin[35] although mev-1 and daf-16 appear to be indepednent.[35]

Beyond the possible roles in longevity, autophagy promotion from curcumin is thought to be protective against gliomas[36][37] as glioma cells are resistant to apoptosis but readily destroyed by autophagy.[38][39] Parkinson’s pathology may be attenuated with curcumin via preservation of autophagy[40]

Curcumin appears to induce autophagy secondary to beneficial modulation of mTOR and ERK1/2 signalling (inhibition and activation, respectively) which may underlie both longevity promoting and select anti-cancer effects

3.2. Interventions

In drosophilia, curcumin can induce longevity via antioxidative properties[35] independent of caloric restriction yet is not complementary with caloric restriction (suggesting acting upon the same pathway)[41][42][43] with most efficacy at 100mM of the feed.[41] Interesting, administration of curcumin for an entire lifespan has been shown to have a possible suppressive effect on longevity but administration for youth (drosophilia health span, which is about the first 30% of life) prolonged median and maximum lifespan by 49% while administration during middle age (up to 45% of lifespan) had less promotion and administration in older age (senesence) reduced median lifespan by 4% (although maximum still increased 11%).[41]

Curcumin has been shown to promote longevity independent of caloric restriction in fruit flies, and appears to have more potency in youth than in older individuals (where some suppressive effects on lifespan are noted)

The metabolite of curcumin, tetrahydrocurcumin, appears to promote longevity in male mice by 11.7% at a dietary intake of 0.2% tetrahydrocurcumin, but is dependent on administration as youth.[44] This study failed to note an effect when mice started curcumin feeding at 19 months (the above results noted with earlier feeding at the 13th month), suggesting the youth requirement extends to mammals.[44] Longevity enhancement in mice has been noted elsewhere.[45]

Conversely, one mouse study has noted a failure of curcumin to enhance lifespan when given at similar doses and times in F1 hybrid mice, despite caloric restriction being effective[46] and lifetime administration of curcumin (0.2%) starting at 4 months has also failed to promote lifespan in UM-HET3 mice.[47] Assuming a food intake of around 8.55g/45g bodyweight[48] and body weights around 45g for the majority of the life[46][47][44] an estimated intake of curcumin daily would be 17.1mg (converting to 380mg/kg bodyweight and an estimated human dose[49] of 22.8mg/kg or 1.5g for a 150lb person)

There is some promising, but currently mixed, evidence to support the role of curcumin in anti-aging. This may follow the same motifs of requiring ingestion of curcumin in youth or at least prior to midlife,

It is an unproven but attractive theory that curcumin works via Chaperone-mediated autophagy (covered on the Longevity page) due to both being prolongevity yet less effective in aged subjects (due to decreasing LAMP-2A expression)

4. Cellular Mechanisms

Curcumin is able to induce effects either directly (the first domino in a series) or downstream of the primary effect (subsequent dominoes). This section serves to differentiate the two and harmonize mechanisms.

4.1. Direct

AP-1, a class of transcription factors made of dimerizations of c-Fos, c-Jun and related proteins that is involved with cell proliferation, survival, and differentiation[50] bind to their receptor on the cell nuclear (TPA response element) to induce effects associated with AP-1.[51][52] The effects of AP-1 differ depending on the proteins that make it up, but curcumin is able to interfere with the AP-1 released by tumor promoters[53] and is able to enhance some phase II (anti-oxidant) enzymes by moderating some better AP-1 confirmations.[54]

Curcumin is also seen as a direct mTOR inhibitor, able to prevent the association of the raptor subset with the TOR protein, inhibiting mTORC1 activity directly without significant influence from AMPK-TSC or Protein Phosphatase A2.[55][56]

Curcumin can also directly inhibit DNA polymerase lambda,[57] focal adhesion kinase (FAK),[58] Src,[58] Protein Kinase C,[59] p300 (CREB Binding Protein),[60] Thioredoxin reductase,[61] Lipoxygenase (LOX),[62] and tubulin.[63]

It may also directly affect (negatively) 17beta-HSD3[64] and 5-alpha reductase.[65]

Curcumin has been noted to directly and potently inhibit the Glycogen Synthase Kinase-3? (GSK3?) enzyme with an IC50 of 66.3nM.[66]

4.2. Junction points

Junction points are defined as proteins or receptors that, by their activation or inactivation, influence a great deal of related proteins.

nF-kB, a proinflammatory transcription factor, is inhibited by curcumin via a two-fold mechanism of preventing p65 translocation to the nucleus, and by preventing the degradation of the molecule which holds nF-kB in a dormant state, IkB.[67] The co-activator of nF-kB, Notch-1, is also suppressed by curcumin although abnormally high levels of Notch-1 can reduce the inhibitory effects of curcumin on nF-kB.[68] nF-kB moderates over 200 related proteins related to cell proliferation, invasion, metastasis, chemoresistance, and/or inflammation.[69][11]

As mentioned previously, the proteins of AP-1 are also seen as a sort of junction point mediating cell proliferation and survival.[50]

4.3. Indirect/Downstream

The main proteins and molecules that are downstream of nF-kB, and thus are reduced in potency when nF-kB is inhibited, are Bcl-2, Bcl-xL, cyclin D1, interleukin-6 (IL6), cyclooxygenase 2 (COX2) and matrix metallopeptidase-9 (MMP9).[70][71][72]

5. Cardiovascular Health

5.1. Cardiac Tissue

Curcumin is suspected to be able to protect against cardiac hypertrophy, inflammation, and thrombosis via inhibition of the protein p300, a Histone acetyltransferase (HAT) and it’s downstream pathways. This inhibition has been shown to prevent heart failure in rats.[73]

5.2. Endothelium

Via induction of Heme-Oxygenase 1 (HO-1), curcumin can prevent the endothelial (blood vessel) dysfunction associated with high blood glucose in a dose dependent manner and may offer protection from side-effects associated with diabetes.[74] In an animal model of diabetes, curcumin has also preserved a degree of endothelial health during disease progression (although it was unable to, at 200mg/kg bodyweight, prevent changes).[75]

This protective effect has also been demonstrated with LPS insult, a pro-inflammatory condition, and curcumin dosed at 50-100mg/kg bodyweight in rats;[76] changes in endothelial contractability (via TNF-a) have also been reduced with curcumin.[77] Protection from L-NAME induced hypertension has also been seen.[78]

In regards to blood pressure, one human study has noted significant decreases in blood pressure but was conducted in a nephritic disease state.[79] Not much human evidence looks at the effects on blood pressure in otherwise healthy individuals.

Appears to hold protective effects on blood vessels, but its clinical significance is not known; seems promising, and most likely mediated through Heme Oxygenase-1

5.3. Triglycerides

500mg curcumin daily has been shown to reduce triglycerides by 47% (110+/-21mg/dL to 58+/-9mg/dL) over 7 days, while a higher dose of 6g reduces triglycerides by 15% (93+/-13mg/dL to 79+/-11mg/dL); the cause for the lowered efficacy of high doses is not known.[80] These were seen in otherwise normal weight and healthy young subjects.[80]

5.4. Cholesterol

500mg curcumin daily has been demonstrated to reduce total cholesterol levels by 17% while a higher dose of 6,000mg reduces total cholesterol by 5% in otherwise healthy subjects.[80]

6. Interactions with Neurology

6.1. Cognition

One study assess curcumin and cognitive injury noted that, in control rats that were not injured, curcumin at 500ppm was able to increase BDNF levels to approximately 140% of control; this was independent of significant changes to CREB (105%) and phosphorylated CREB (93%).[81]

6.2. Stress

In vitro, curcumin can abolish the induction of the NMDA receptor subunit R2B mRNA by corticosterone[82] when corticosterone is incubated at 0.1mM and curcumin at concentrations as low as 0.62uM;[83] this may be related to the ability of curcumin in vitro to prevent corticosterone-induced neuronal death.[83]

Curcumin at 5, 10, and 20mg/kg was fed to rats daily for 21 days, and upon being subject to acute stress and subsequent cognitive testing; curcumin dose-dependently reduced the negative influence of stress on spatial memory with both higher doses (10, 20mg/kg) being significant and slightly less effective than 10mg/kg imipramine.[83]

6.3. Neuronal Injury

Curcumin at 500ppm in rats (a dose similar to some anti-Alzheimer’s dosages[84]) for 4 weeks on either a high fat or normal diet who were then subject to a fluid percussion injury noted that the increased oxidation in the brain (139% normal diet, 239% high fat diet; high fat did not induce oxidation without neural injury) was reduced to 45-47% in both groups and BDNF was normalized despite its inherent reduction in neural injury,[81] and other proteins that tend to be reduced in this form of injury are somewhat normalized with curcumin.[85] Cognitive performance was declined after injury, and the reduction was attenuated but not normalized.[81]

6.4. Alzheimer’s Disease

Curcumin is able to inhibit aggregation of beta-amyloid proteins in the brain, and thus prevent neural inflammation which would normally be downstream from said aggregation. The former has been noted in vivo[86] and has been hypothesized to be the reason as to why higher circulating levels of Beta-Amyloid have been noted (statistically insignificant) with curcumin supplementation[87] as beta-amyloid is prevented from aggregating in the brain,[88] and thus must circulate somewhere.

Mechanistically, curcumin may be able to reduce Beta-amyloid build-up in neural tissue

In a rodent model with advanced Alzheimer’s Disease characterized by beta-amyloid accrual, curcumin was able to attenuate the decline in neural performance and was synergistic with DHA; a component fatty acids from Fish Oil.[89] This synergism may be related to how both agents can reduce beta-amyloid aggregation, but by differing mechanisms;[90][91] some authors hypothesize that this synergism may be further enhanced by exercise[92] due to an interaction with exercise and fish oil on neuronal plasticity.[93]

A 6-month trial has been conducted on Curcumin and Alzheimer’s, using basic curcumin at either 1 or 4g daily for 6 months in a population of 50+ year old chinese persons suffering from cognitive decline for at least 6 months prior to trial onset. Scores on the MMSE, a rating scale for Alzheimer’s, increased progressively in the placebo (indicating cognitive decline) but were mostly static in both curcumin groups.[87] This trial is limited in statistical power due to its sample size of 27 completions and multiple confounds, however.[87]

Some therapeutic promise, but evidence is limited

7. Implications for Digestion and the Intestines

Curcumin tends to be most relevant to the colon due to its poor oral bioavailability. Oral bioavailability is a measure of how much of a molecule as a percentage is absorbed from the gut, and whatever is left over (in this case, a large amount) is carried on to the colon where it may interact with colonic microflora or the colonic walls.

7.1. The Colon and Ulcerative Colitis

One double-blinded multicenter study noted that, in conjunction with standard therapy for Ulcerative Colitis, 2g of curcumin daily (1g with two different meals) was able to confer significant protection against colonic inflammation and improve symptoms of Ulcerative Colitis for as long as it was used.[94] Less mortality and relapse was noted with curcumin usage, but the difference was not significant 6 months after cessation of usage like it was for the 6 months it was being used for.[94] These effects were seen earlier in both Ulcerative Colitis and Crohn’s Disease, two human conditions associated with intestinal inflammation.[95]

8. Interactions with Glucose Metabolism

8.1. Mechanisms

In liver cells, Curcumin at 20uM appears to activate Adenosine Monophosphate Kinase (AMPK) to the same degree as Metformin (2mM), which is 400-fold more potent on a concentration basis.[96] Although glucose uptake into cells tends to be secondary to AMPK activation[97] and has been noted with both Metformin and another potent AMPK activator Berberine, this study noted that Curcumin failed to induce glucose uptake, instead noting a trend to reduce glucose uptake.[96] This inhibition of glucose uptake has been noted elsewhere, where 100uM Curcumin was shown to inhibit insulin-stimulated GLUT4 translocation[98] despite curcumin twice being shown to not significantly interact with the insulin receptor itself (not cell type specific).[99][96]

Remarkably potent AMPK activator, yet seems to fail at inducing glucose uptake into cells (and thus undermines many of the inherent benefits of AMPK as it pertains to diabetes)

8.2. Blood glucose

The effect of curcumin to lower blood glucose was one of the first effects to be seen with curcumin, seen in 1972.[100][101]

One of the mechanisms of this blood glucose lowering effect is by stimulating Adenosine Monophosphate Kinase (AMPK) in skeletal muscle, drawing in glucose.[102] This effect is enhanced with the presence of insulin, and since insulin also activates the PI3K pathway curcumin appears to be synergistic with insulin in regards to reducing blood sugar levels.[103] Curcumin can also activate AMPK in other cells, such as liver cells[96] and some cancer cells.[104]

8.3. Diabetes

Curcumin is able to alleviate the downstream inflammatory reactions that occur during times of diabetes and metabolic syndrome in rats[105] and, vicariously through its anti-inflammatory effects, improve insulin resistance.[106][105]

9. Interactions with Fat Mass

9.1. Mechanisms

Curcumin has been noted to attenuate lipolysis induced by TNF-? and isoproterenol (representative of catecholamines) in 3T3-L1 adipocytes, which was thought to be secondary to suppression of ERK1/2 activation.[107] ERK1/2 is known to be regulated by AMPK[108] which curcumin has been found to activate[109] (in liver cells, this was noted to be of comparable potency to Metformin but requiring 20uM to Metformins 2mM[96]); all of these events being similar to the known AMPK activator Berberine.

Fatty Acid Synthase (FAS) is inhibited by Curcumin with an IC50 of 26.8?M (59.1?M in regards to ?-ketoacyl reduction); the inhibition was noncompetitive when NADPH was the substrate, but mixed competitive with either acetyl or malonyl Coenzyme A[110] and had both slow and fast acting components in a concentration and time dependent manner.[110] 20uM of Curcumin abolished lipid accumulation in isolated 3T3-L1 cells undergoing differentiation, which may have been due to downregulation of PPAR? and CD36;[110] another study notes that PPARy activation by Curcumin is dependent on AMPK activation.[109]

Curcumin appears to be a potency activator of AMPK

9.2. Inflammation (Adipose Tissue)

Inflammation appears to play a role in obesity, particularly one cytokine known as TNF-?; adipose of genetically obese mice overexpress TNF-? which is also seen in adipocytes of overweight individuals[111] and TNF-? expression appears to negatively correlate with LPL activity.[112] TNF-? itself does exert lipolytic activity,[113] so its elevation in obesity may be as a biomarker of underlying dysregulation rather than a per se contributor; the possibility of TNF-? resistance (a phenomena similar to insulin resistance, as TNF-? has its own receptor class on adipocytes[114]) also being possible.[111] TNF-? is a potent activator of nF-kB (nuclear receptor) which mediates many of its effects,[115] and overactivity of nF-kB and TNF-? in adipocytes are both highly correlated with metabolic syndrome and obesity.[111]

In general, excessive inflammation in adipocytes (assessed by looking at biomarkers thought to be representative of inflammation such as TNF-?) is highly correlated with obesity and metabolic syndrome; interventions which reduce inflammation in adipocytes tend to also be those that can reduce fat mass in persons suffering from excessive inflammation

A reduction in immune cell infiltration in adipose tissue has been noted in vivo when mice are given 3% curcumin in the diet for up to 4 weeks, as assessed by histological examination.[105]

9.3. Adipokines

Curcumin appears to be associated with an increased FOX01 transcription activity and increased adiponectin production in vivo (with higher circulating levels of adiponectin noted in both genetic and diet induced obesity, but lean control mice did not experience an increase);[105] FOXO1 is known to positively influence adiponectin transcription in fat cells.[116][117]

Leptin secretion from adipocytes appears to be suppressed with 12 and 24 hour incubation with Curcumin in a concentration and time dependent manner.[118]

9.4. Interventions

In obese mice given curcumin (3% of feed), despite noting an increase in food intake relative to control; this reduction in body fat was not observed in normal mice.[105]

9.5. Side-effects related to Obesity

In a study on rats, sympathetic activation from circulating fatty acids (commonly seen in obesity) is reduced via curcumin’s lipid lowering effects; the resulting state is cardioprotective independent of weight loss.[119]

Curcumin can also suppress angiogenesis in rat fat cells, a longer term adaptation associated with prolonged obesity.[120] This is a general mechanism that applies to more cell types as well.[121]

10. Oxidation and Anti-Oxidation

When comparing 500mg curcumin against 6g curcumin, the anti-oxidative potential of the two does not significantly differ; if anything, 500mg curcumin seems superior due to insignificantly higher AUC of the increase in anti-oxidant abilities as measured by ORAC.[80] This is thought to be due to a possible pro-oxidant effect of curcumin at higher dosages, seen with other anti-oxidants.[122][123]

11. Interactions with Inflammation and Immunology

11.1. Mechanisms

One of curcumin’s most well-researched effects on inflammation is inhibiting TNF-a induced activation and nuclear translocation of nF-kB, a protein that influences the genetic code to produce inflammatory cytokines. This has been seen in immune cells after oral ingestion of 150mg curcumin (Resveratrol at 75mg, Green Tea Catechins at 150mg, and soy at 125mg as confounders)[124] but also in isolation in vitro[125] and in vivo.[126][127][128][129] Activation of nF-kB can increase protein content (amounts) of Cyclooxygenase-2 (COX-2), a pro-inflammatory enzyme; pretreatment with curcumin reduces COX-2 upregulation induced by inflammatory cytokines.[130] Other pro-inflammatory enzymes that are suppressed by curcumin are iNOS, LOX (directly inhibited), and Phospholipase A2 (directly.)[131]

Curcumin appears to be able to suppress most adhesion molecules investigated, including E-selectin and P-selectin, ICAM-1, VCAM-1, and ELAM-1, the latter three are due to nF-kB inhibition downstream of Akt.[132][133]

Curcumin can reduce inflammation through a variety of means; preventing pro-inflammatory signals from acting on the nucleus (nF-kB related), reducing the ability of immune cells to get to sites of inflammation (adhesion related), and reducing the exacerbation of already present inflammation by reducing the activity of inflammatory enzymes (COX2, LOX related).

11.2. Treatment of Arthritis

Curcumin is associated with reducing a variety of inflammatory signals, and a lot of them that are associated with arthritis and inflammatory joints.[134]

When dosed equally (200mg/kg in rats), curcuminoids from turmeric are 4.6-8.3% more effective than the active components of Ginger in suppressing inflammation associated with cytokine release in arthritis.[135] Both herbs are more potent than indomethacin.[135]

12. Bacteria and Viral interactions

12.1. Virus replication

One study found that curcumin was able to suppress replication of the Rift Valley fever virus and its fully virulent form (ZH501) in vitro.[136] A modification to the IKK-? protein (which inhibits I?B? and serves to enhance nF-kB signalling) keeps IKK-? in an active state and exacerbates inflammatory signalling, curcumin can bind to IKK-? and allow I?B? to suppress nF-kB activation and inflammation, which prevents virus replication.[136]

13. Implications in Cancer Metabolism

13.1. General (Not mechanisms)

Curcumin has the ability to protect DNA from oxidation via the heavy metal arsenic[137], and this protection has been demonstrated in human trials after oral ingestion 1g of a 20:1 curcumin:piperine (Black Pepper) combination for 3 months.[138] Blood lymphocytes were the biomarker for DNA damage.

In rats fed a low dose of curcumin (0.03% of the diet), curcumin was able to prevent formation of adducts in hepatic DNA induced by an injection of the carcinogenic benzo(a)pyrene.[139] Curcumin also prevented adducts in colonic cells when administered at 2% of the diet with meals.[140]

13.2. General (Mechanisms)

One of the mechanisms under investigation for chemoprotective effects of curcumin is the inhibitory effect on nF-kB, a protein that can influence genetic coding and transcription when activated. Normally, TNF-a (a pro-inflammatory cytokine) positively influences nF-kB activity and induces cell growth, survival, and inflammation. Curcumin can inhibit the interaction between the two molecules without reducing TNF-a levels, and aside from the inhibition of cytoprotection the elevated levels of TNF-a can induce cellular death via Fas-associated protein cell death and caspase-8.[141] This mechanism appears to ‘sensitize’ cells to cell death induced by TNF-a by inhibiting cellular survival via nF-kB[142][143] and is most likely due to curcumin’s ability to prevent or reduce activation of p38 in the face of other activators.[144][145][146]

Curcumin is also able to suppress a transcription factor associated with nF-kB, the Notch family of proteins; this potentiates the suppressive effects on nF-kB, but Notch-1 overexpression is able to act in reverse and attenuate curcumin’s suppressive effects on nF-kB.[68]

Other notable products downstream of nF-kB that are reduced by curcumin administration are cyclooxygenase-2 (COX-2), cyclin D1, adhesion molecules, MMPs, inducible nitric oxide synthase, Bcl-2, Bcl-xL, and tumor necrosis factor (TNF); most of which are associated with cancer metabolism in some manner.[72][71][130] Curcumin appears to directly inhibit IKK? as the method of reducing nF-kB translocation.[147]

In a B-CLL cell culture, curcumin was able to induce apoptosis with an IC50 of 5.5uM while its effects in healthy mononucleated (non-cancerous) cells were associated with an IC50 of 21.8uM.[125]

13.3. Prostate Cancer

Secondary to inhibiting expression of the cytokines CXCL1 and CXCL2 (a downstream effect of nF-kB translocation inhibition), curcumin appears to negatively regulate several factors that can lead to prostatic tumor meta-stasis (COX2, SPARC and EFEMP) which can lead to less metastasis in vivo.[147] As siRNA inhibition of CXCL1/2 also had these effects, this appears to be the metabolic lever of concern.[147]

14. Interactions with Hormones

14.1. Testosterone

Curcumin, at 100mg/kg bodyweight in rats, has been shown to preserve testosterone levels when coadministered with a drug (Metronidazole) that causes testosterone reductions and worsens parameters of sperm.[148]

Protective effects on the testes have also been noted with curcumin in regards to alcohol, where curcumin (80mg/kg bodyweight) was able to preserve testicle structure and testosterone levels despite alcohol consumption,[149] most likely though preventing the oxidation of ethanol to acetylaldehyde.[150] Other compounds that damage the testicles and reduce testosterone, but are protected against by curcumin, include excessive chromium levels[151] and cadmium.[152]

When looking at the 17beta-HSD3, the final step in testicular testosterone synthesis, curcumin was found to be a noncompetitive inhibitor with an IC50 of 2.3uM, and brought Luteinizing-Hormone stimulated testoterone levels down to 34% of control at a concentration of 10uM.[64] This effect was not dose-dependent, and concentrations of 1uM were not significantly different from 0.1uM and control cells.[64]

Curcumin may also possess inhibitory actions against 5-alpha reductase, the enzyme that converts testosterone into the more potent androgen DHT. The IC50 value is reportedly between 5-10uM.[65]

Given the above two mechanisms (17beta-HSD3 and 5AR inhibition) are anti-androgenic in nature, it would be prudent to observe in vivo effects of curcumin. The only current study on the matter used injections of PEG-curcumin at 0.5mg (giving a Cmax of 7ug/mL to then decline to 1ug/mL) noted a decrease in circulating testosterone levels and function of seminal vesicles, although testicle weight did not decline.[153]

In regards to aromatase, the enzyme that converts testosterone to estrogen (and thus higher activity would mean a more anti-androgenic profile), curcumin does not directly inhibit aromatase in vitro[154] but appears to reduce the catalytic activity of aromatase (also known as CYP1A) in mice.[155] Clinical relevance of these effects is not known.

Curcumin appears to have protective effects on testicular functions, but possesses anti-androgenic activity. The concentration required for inhibition is high, but it appears to occur in vivo when it is met; it is uncertain what oral dose is needed for these effects, but it might occur with superloading and increasing bioavailability. Low doses of curcumin may have no adverse effect whatsoever

14.2. Estrogen

In regards to possible anti-estrogen effects, the lack of inhibition on aromatase[154] but potential to reduce catalytic activity of aromatase[155] suggests some interactions may exist at this stage. One study comparing normal rats versus a Menopausal model (ovariectomized) noted that 10mg/kg oral ingestion in the normal mice was able to reduce circulating estrogen levels.[156]

100nM of Curcumin is able to act as an agonist at estrogen receptors in MCF7 breast cancer cells, but has low activation of target genes relative to estradiol, although more potent than Quercetin and Enterolactone (from Sesamin).[157] It is possible that Curcumin may act as a Selective Estrogen Receptor Modulator (SERM) and compete for the more potent estradiol, as it has been noted to reduce estrogen-induced cell proliferation elsewhere (was not tied directly to the estrogen receptor in this study).[158]

In regards to anti-estrogenic activity, limited but theoretical potential of Curcumin to be antiestrogenic via either reducing the effects of aromatase or via acting as a SERM (not yet wholly established)

A pegylated curcumin derivative (similar bioactivity, designed for ingections) at 500mg in rats is able to exert estrogenic effects as assessed by sex organs (uterine changes indicative of estrogenicity in females).[153]

High doses appear to be estrogenic

15. Interactions with Skeletal Muscle

15.1. Acute Protective Effects

Through it’s anti-oxidant effects, curcumin can ameliorate oxidative damage to skeletal muscle via Ischemia/Reperfusion when preloaded at 100mg/kg (I.P injection) to rats, with a potency greater than Vitamin E.[159] Curcumin also ameliorates the increase in inflammatory cytokines associated with Ischemia/Reperfusion injury.[159][160]

As for the mechanisms of the above, curcucmin (5-10uM) appears to increase Glucose-Regulated Protein 94 (Grp94) expression, which regulates calcium homeostasis; this regulation of calcium homeostasis appears to precede the standard inhibition of nF-kB activation and reduce the state of oxidation when an oxidative insult is produced.[161] Interestingly, curcumin can also inhibit upregulation and damage from lead via preventing Grp94 upregulation,[162] and general protection against cadmium as well.[163]

15.2. Catabolism/Anabolism

Curcumin (via injection) is also implicated in increasing the recovery of skeletal muscle capacity associated with deloading, although it was not able to preserve skeletal muscle mass during deloading.[164] These results differ from earlier ones showing a 100mg/kg oral dose of curcumin in rats was able to reduce muscular atrophy while a higher dose of 250mg/kg actually improved skeletal muscle weight.[165]

Curcumin is able to inhibit Atrogin1/MAFbx and its subsequent ubiquitin ligase activity in vitro at 25uM,[166] which induces skeletal muscle catabolism downstream of p38/MAPK induced by TNF-a. This has been confimed in rats with injections of 10-60ug/kg curcumin daily for 4 days which preserved lean mass in the face of LPS, by preventing p38 activation and the subsequent Atrogin1/MAFbx activation.[166]

15.3. Glucose metabolism

Skeletal muscle, via glucose uptake and oxidation, is a tissue regulator of glucose metabolism.

Some fatty acids, such as palmitic acid, can activate (phosphorylize) IRS-1 which causes negative feedback to the insulin receptor and desensitizes muscle cells to insulin-stimulated glucose uptake; curcumin appears to prevent this from occurring.[167] This effect is shared by Green Tea Catechins.[167] Improvements in this mechanism of insulin resistance have been seen in vivo with dose-dependent oral doses of curcumin at 50, 150, and 250mg/kg bodyweight.[168] AMPK activation appears to be a key intermediate in these effects.[168][102] Beyond acting upon IRS, curcumin may also increase glucose uptake into skeletal muscles by acting on muscarinic acetylcholine receptors and then through PLC and PI3K.[169]

Curcumin has been implicated in reversing some abberations in skeletal muscle associated with type II diabetes, such as upregulation of beta-adrenergic receptors and Akt,[170] the downregulation of NRF2 and Heme Oxygenase-1,[171] and downregulation of AMPK and CPT-1.[168] At least one study has suggested that the state of diabetes may be a prerequisite, and although it didn’t measure all above parameters it did note no effects of curcumin in non-diabetic mice.[172]

16. Interactions with other Organ Systems

16.1. Liver

Curcumin appears to be able to reduce diet-induced liver fat builded (steatohepatitis) at 0.15% of the diet which is thought to be secondary to activation of AMPK and induction of PPAR?.[173]

16.2. Kidneys

At least one human intervention showed that curcumin was able to suppress diabetic nephropathy (related to kidney function) and decrease proteinuria at a dose of 500mg turmeric (22.1mg curcumin) thrice a day with meals for 2 months. The mechanism of action appears to be suppressing pro-inflammatory cytokines like TGF-b and IL-8. These benefits have been shown to extend to nephritis associated with lupus at the same dosing protocol in humans.

Curcumin exerts this apparent kidney protection via suppressing inflammation and related cytokines or mRNA associated with inflammation (MCP-1, IL-8, nF-kB). Curcumin at 5mg/kg bodyweight (rats) is able to prevent histological changes (related to macrophage infiltration) in kidney structure associated with experimental LPS injections when administered simultaneously and in delaying the inevitable progression of renal failure.

Some protective changes are also present, as curcumin can upregulate Heme-Oxygenase 1 in kidney cells partially via nF-kB suppression and this mechanism is linked to kidney protection effects.

Demonstrated to have protective effects on the kidneys in clinical settings, and animal studies suggest this may extend to preventative measures as well

17. Nutrient-Nutrient Interactions

17.1. Piperine

Pairing Curcumin with Piperine, a Black Pepper extract that is also an inhibitor of glucuronidation enzymes in the intestines and liver, is able to increase bioavailability 20-fold (2000% of baseline values) when 20mg piperine is paired with 2g curcumin.

The pairing of the two has been demonstrated synergistic in attenuating benzo(a)pyrene toxicity in various tissues[179][180] as well as mitigating DNA damage.

Interestingly, this synergism does not seem to apply to preventing hypertension induced by L-NAME; both compounds are effective in attenuating high blood pressure from a lack of Nitric Oxide, but their effects are not even additive.

17.2. Ginger

Ginger and Turmeric are both plants in the same family of plants, and may have related phytonutrient profiles due to this association.

One study investigating the combination of 6-gingerol enhanced ginger and turmeric topical solution (at 3% and 10% respectively) found enhanced wound healing with both compounds in isolation and slightly better recovery with the combination, although not synergistic.

The combination appears to be more effective than either compound in isolation in suppressing some adverse blood parameters associated with metabolic syndrome, such as high blood sugar and lipids.

17.3. Soy Isoflavones

The soy isoflavones, particularly genistein and daidzein, appear to be synergistic with curcumin as it pertains to reducing androgen receptor content and circulatin Prostate-Specific Antigen (PSA) levels in otherwise healthy men; insinuating the combination could be useful against prostate cancer. The dosages used were fairly low in this study, 40mg of isoflavones (66% daidzein, 10% genistein) and 100mg curcumin daily for 6 months, and dropped PSA from 18.8+/-12.4 to 10.2+/-6.2ng/mL.

17.4. Docosahexaenoic acid

One component of Fish Oil, docosahexaenoic acid (DHA), exert synergistic effects in anti-cancer signalling in breast cancer cells which is apparently unique when looking at the mechanisms of either compound in isolation. This synergism apparently extends over into each compounds anti-inflammatory effects, and this mechanism extends to EPA.

17.5. Vincristine

Curcumin at 1uM concentration in cancerous leukemia cells has been shown to synergistically enhance the actions of Vincristine, an alkaloid isolated from Madagascar Periwinkle (not to be confused with Vinpocetine, from another species of Periwinkle). This occurred in 4 out of 5 samples when Vincristine was incubated at 10uM.

17.6. Rolipram

Curcumin shows synergism with Rolipram (a potent PDE4 inhibitor); PDE4 inhibitors increase cAMP levels via PKA in cancerous leukemia cells. Additive in 1 out of 5 tested samples and synergistic in the other four.

A nutraceutical PDE4 inhibitor (at the moment, synergism untested) is Resveratrol.

17.7. Iron

A wide variety of phenolic compounds (of which curcumin is one) are able to bind to dietary non-heme iron and inhibit its absorption; this is seen with Green Tea Catechins and Quercetin mostly. Curcumin has been found to interact with some ions after digestion.

When testing for the interaction of turmeric and iron, whole turmeric at 0.5g was found to not adversely affect iron absorption.

17.8. Itself

Curcumin is one of the four curcuminoids, a curcuminoid being defined as a molecule with two ferulic acid moieties bound together. At least one study has looked at the effects of each ingredient in isolation and the combination, and in regards to its nematocidal effects the four curcuminoids show synergism with each other.

17.9. Garcinol

Garcinol is a polyisoprenylated benzophenone chalcone molecule that is found in Garcinia Indica, a plant in the mangosteen family of fruits. It was found synergistic in inducing apoptosis in pancreatic tumor cells with an apparent synergism 2-10 fold higher than the sum of the two.

18. Safety and Toxicology

18.1. General Safety

According to human interventions investigating anti-cancerous effects of curcumin, doses up to 10g daily of curcumin are not associated with any acute or salient signs of toxicity. When using enhanced formulations to increase circulating levels of curcumin, 1g of MERICA (Curcumin bound to lecithin) over 8 months is not associated with any side-effects.

18.2. Side-effects

Dosages of 6g daily have been associated with minor flatulence and a yellowing of the stool, both of which stopped after supplement cessation.

Jiang Xiang – Dalbergia heartwood – “Descending Fragrance”

Nature: acrid, warm

Enters: Heart, Liver, Spleen, Stomach

Actions: Promotes blood and Qi circulation, dispels blood stasis; stops bleeding; relieves pain.

Indications:
• Blood stasis: pain in the chest, hypochondria, pain and bleeding in trauma, fractures, sprains, contusions.
• Spleen and stomach Qi stagnation: epigastric and abdominal pain.
• Topical: for lacerations.
• Coronary heart disease.
• Bensky/Gamble classifies this with herbs that stop bleeding.
HF: An An Shen (spirit calming) herb, important in Gu Zheng (Gu parasite) formulas (because of emotional disturbance common in patients with Gu).

Dose: 6-9g (1.5-3g directly as powder)

Liu Ji Nu – Artemisia anomala – Anomala – “Liu’s Resident Slave”

Nature: bitter, warm

Enters: Heart, Spleen

Actions: Dispels blood stasis; unblocks menstruation; alleviates pain.

Indications:
• Blood stasis: amenorrhea, post partum abdominal pain; falls, fractures, contusions, sprains.
• Acute viral hepatitis: icteric or anicteric phase. Rapidly improves the appetite.
• Topical: as a powder/ointment for contusions, bleeding from wounds, and especially burns. In one study, an ointment made from the herb was beneficial in treating all 24 cases of second- and third-degree burns, with healing occurring in three days to three weeks.

Dose: 3-9g

Lu Lu Tong – Sweetgum fruit – Liquidambar – “All Roads Open”

Nature: bitter, neutral

Enters: Liver, Stomach

Actions: Promotes blood and Qi circulation; opens the middle Jiao; unblocks the channels; promotes urination.

Indications:
• Stagnation: Epigastric pain, abdominal distention, irregular, scanty menses.
• Wind-damp Bi syndrome with pain and stiffness of the lumbar region and knees.
• Edema with difficult urination.
• Doctrine of signatures: resembles a pollen grain or mast cell – useful for allergic disorders. Also, Li: its tiny points indicate its ability to guide to small places (sinuses, channels, etc.).
Hsu: Anti-allergic effect, cures urticaria and allergic rhinitis.

Dose: 3-9g

Mao Dong Qing – Ilex root – Rough-haired Holly – Ilex pubescentis

Nature: bitter, astringent, neutral

Enters: Heart

Actions: Clears heat and toxicity; invigorates blood circulation; promotes flow of the channels.

Indications:
• Wind-heat EPI.

• Lung heat: cough, water distention in the larynx, swollen painful throat, tonsillitis.

• An ingredient in the popular patent remedy Gan Mao Ling.
• Dysentery.
• Coronary disease; thrombotic infarction; vasculitis.

• Topical: burns.
• Anti-tussive; bacteriostatic; expectorant; hypotensive; dilates coronary arteries; probably has antiviral properties.
Dose: 30-120g (to 500g for phlebitis)

Meng Chong – Tabanus – Gadfly

Nature: bitter, slightly toxic, slightly cold

Enters: Liver

Actions: Powerfully promotes blood circulation and removes blood stasis.

Indications:
• Blood stasis: amenorrhea, traumatic injury, masses.
• May cause diarrhea (which can be beneficial if there is blood stasis in the intestines).
• This is the strongest herb to promote blood circulation in the pharmacopeia.
Hsu: Anticoagulant and hemolytic effects.

Dose: 1.5-3g

Mo Yao – Myrrh – Commiphora myrrha resin

Nature: bitter, neutral

Enters: Heart, Liver, Spleen

Actions: Promotes blood circulation, dispels blood stasis, relieves pain; relieves swelling; promotes tissue regeneration; relaxes the tendons.

Indications:
• Blood stasis: dysmenorrhea, amenorrhea, epigastric pain, Bi syndrome, traumatic injury, carbuncle pain, appendicitis, immobile abdominal masses, abdominal pain, chest pain, sores, swellings.
• Topical: non-healing carbuncles, ulcers, sores.
• Stomatitis, gingivitis, laryngitis.
• Stronger for severe pain (e.g. angina pectoris) than Ru xiang.
• Better than Ru xiang at removing blood stasis.
• May lower cholesterol and prevent plaque.
• Stimulates gastrointestinal motility.
• Antifungal.
• Fry with vinegar to enhance its blood circulating properties.
• Related to the Ayurvedic herb Guggul.
JC: Tonic, stimulant, powerful antiseptic and disinfectant (mucus membranes), vulnerary (healing), expectorant, emmenagogue, astringent, carminative, purgative (large dose), cardiac stimulant.
• Increases WBC count.
• Enhances the eliminative function of the mucus membranes of the bronchi and genitourinary tract.
DY: The uncooked herb is irritating to the stomach and mucus membranes.
Yoga: Bola: K, V-; P+ (in excess)
• Bitter, astringent, sweet/heating/pungent.
• Alterative, emmenagogue, astringent, expectorant, antispasmodic, rejuvenative, analgesic, antiseptic; prevents decay, reverses aging, rejuvenates the mind and body.
• Closely related to Guggul (Commiphora mukul).
• Dispels old, stagnant blood from the uterus.
K&R: Anti-inflammatory, astringent, immune stimulant, epitheliogenic.
• Metal: clears phlegm from the mucus membranes.
• For bronchitis, urinary tract infections, pharyngitis, gingivitis, skin ulcers.
• Increases WBC count.
PCBDP: Lowers lipids, cholesterol; inhibits platelet aggregation; appears to activate the thyroid gland (animal studies).
IBIS: Anticatarrhal, antimicrobial, antiseptic, astringent, carminative, expectorant, stimulant.
• [Western] Dosage: tincture: 2 – 5 mL.
• Mucous membranes pale and lax; tonsils enlarged and spongy; throat pale and tumid; chronic bronchitis with profuse secretion of mucus or muco-pus, difficult to expectorate; soreness and sponginess of gums; ptyalism; weight and dragging in pelvis in females; leukorrhea; muscular debility (Felter and Scudder, p. 483)
• External: spongy and bleeding gums; sore throat with aphthous or sloughing ulcers; chronic pharyngitis with tumid, pallid membranes and elongated uvula; spongy, enlarged tonsils (Felter and Scudder, p. 483)
• Internal: enfeebled conditions with excessive mucous secretion, especially in the bronchial and renal mucosa; chronic bronchitis; chronic gastritis; atonic dyspepsia (Felter and Scudder, p. 483); pharyngitis; respiratory catarrh; common cold; furunculosis; mouth ulcers; gingivitis (British Herbal Pharmacopoeia, p. 73)
• Contraindicated during pregnancy (Felter and Lloyd, p. 1300) due to its emmenagogue and abortifacient effects (Brinker, Farnsworth)

Dose: 3-12g

 
BII (Guggulipid, from Guggul, Commiphora mukul): Lowers cholesterol and triglycerides – cholesterol typically will drop 14-27% in 4-12 weeks while triglycerides will drop 22-30%.
• Increases the liver’s metabolism of LDL and uptake of LDL from blood.
• Standard dosage is 25 mg of guggulsterone [a component] TID.
• Non-toxic, safe in pregnancy.
• Beneficial in acne vulgaris.
• May inhibit platelet aggregation.
• Useful in atherosclerosis, however the high dosage required of the crude herb or extracts can lead to side effects and therefore pure guggulipid (guggulsterone) should be used.

Chuan Niu Xi – Cyathula root – “Sichuan Ox Knee”

Nature: sweet, bitter, neutral

Enters: Liver, Kidney

Actions: Expels wind; promotes urination, drains dampness; invigorates the channels and blood; disperses blood stasis; directs fire and blood downward; weakly nourishes the liver and kidneys.

 

Indications:
• Stronger to move blood and alleviate pain, but less tonifying than Huai niu xi.
• Pain due to wind-dampness – especially lower back pain.
• Musculoskeletal pain, traumatic injury.
• Atrophy and spasm in the lower extremities.
• Painful urination with blood in the urine.
• Amenorrhea, postpartum abdominal pain, difficult labor, abdominal masses.
• Hematemesis, epistaxis, toothache, ulcers on the tongue and mouth, headache and dizziness associated with fire flaring upward and abnormal bleeding.

Dose: 4.5-9g

Huai Niu Xi – Achyranthes root – “Ox Knee”

Nature: bitter, sour, neutral

Enters: Liver, Kidney

Actions: Promotes blood circulation, dispels blood stasis; tonifies the liver and kidneys; strengthens the sinews and bones, benefit the joints; promotes urination; conducts blood, fire/heat/Yang, and herbs downward; clears damp-heat in the lower Jiao; unblocks the menses.

Indications:
• Blood stasis: irregular menstruation, dysmenorrhea, amenorrhea, abdominal pain after childbirth, traumatic injury, lochioschesis.
• Liver and kidney deficiency: weak, sore lower back, and lower limbs (knees).
• Liver Yang rising, upper body bleeding, or flare-up of fire: hematemesis, epistaxis, toothache, mouth sores, headache, dizziness, bleeding gums, blurred vision.
• Lower Jiao damp-heat: knee pain, lower back damp Bi syndrome, painful urinary dysfunction, vaginal discharge, stones, hematuria.
• Lower Jiao blood stasis (damp-heat): urethral pain, hematuria.
• In its raw form, it is better at promoting blood circulation.
• When it is cooked, it is more tonic. In its raw form it is more blood-moving.
• Lowers blood pressure – sometimes used in very high doses for this purpose.
Hsu: Analgesic, antispasmodic (GI), diuretic, hypotensive (temporary vasodilation), anti-allergic action

Dose: 9-15g

Ru Xiang – Frankincense – Mastic – Boswellia carterii – “Fragrant Milk”

Nature: bitter, acrid, warm

Enters: Heart, Liver, Spleen

Actions: Promotes blood and Qi circulation; relieves pain; relieves swelling; promotes tissue regeneration; relaxes the sinews, invigorates the channels.

Indications:
• Blood stasis: dysmenorrhea, amenorrhea, epigastric, chest, abdominal pain, Bi syndrome, traumatic injury, carbuncle pain, appendicitis, early stages of carbuncles, sores, swellings, wind-damp Bi syndrome, rigidity, spasms, angina pectoris. Often used with Mo yao (in studies, for chest pain).
• Pain, redness, swelling of the gums, mouth, and throat.
• Topical: as powder or ointment to reduce swelling, generate flesh, alleviate pain, and promote healing of non-healing carbuncles, ulcers, and traumatic injuries.
• Can easily exhaust the Qi.
• Better than Mo yao at relaxing the tendons.
• Fry with vinegar to enhance its blood circulating properties.
Hsu: Strong antibacterial properties.
DY: The uncooked herb is irritating to the stomach and mucus membranes.
Ru xiang is superior to Mo yao for simultaneously moving Qi and blood and freeing the flow of the network vessels to treat Bi with loss of articular mobility and contracture of the sinews.

 

Dose: 3-9g

BII: on a constituent, boswellic acids:
• Osteoarthritis: several mechanisms of anti-arthritic action, including inhibition of inflammatory mediators, prevention of decreased glycosaminoglycan synthesis, and improved blood supply to joint tissues.
400mg boswellic acids TID

Examine.com: On Boswellia serrata (the Indian species – though probably there is a lot of overlap, and I think much of this article is not at all specific to the serrata species):

Boswellia Serrata is a gum resin extracted from a tree, which is sometimes burnt (the entire species of Boswellia is commonly known as Frankinsence) as an aromatic or otherwise administered as medicine. It has most usage for medicine in Ayurvedic medicine, some reading into Traditional Chinese Medicine, and its usage extends to the Middle East and other tropical regions.

Boswellia Serrata, via its active boswellic acids, appears to be a novel inhibitory of a pro-inflammatory enzyme called 5-Lipoxygenase and may possess other anti-inflammatory effects (such as nF-kB inhibition, which are not as novel). These anti-inflammatory effects have been investigated for their benefits in osteoarthritis (OA), and it appears that oral Boswellia supplements can suppress pain and immobility associated with OA quite significantly with the effects taking as little as a week to occur. The studies are well conducted, but funded by the producers of the tested supplements. There are limited non-funded interventions with Boswellic for this claim, but they seem to agree with the battery of funded study in effect size.

Remarkably, Boswellia appears to be quite anti-cancer that appears to be more anti-proliferative rather than apoptotic (the latter meaning to induce regulated cell death) since it is a potent inhibitor of angiogenesis and cell invasiveness. There are not a large battery of studies on these claims, but preliminary mouse and rat evidence where the rodents are injehttp://chineseherbinfo.com/wp-admin/post.php?post=647&action=editcted with tumors suggest that Boswellia can potently suppress tumor growth (Pancreatic, Colorectal) and in some cases actually outright prevent tumor growth (Prostatic, Glioma). Boswellia appears to be a very promising anti-cancer herb due to the potency it exhibits in animals, with one study noting this after oral administration (100mg/kg of the main boswellic acid in animals). The potency has been replicated in other cancer cell lines in vitro (including breast, cervical, myeloma and leukemia) but these cancers do not yet have animal interventions yet.

Boswellia appears to be fairly nontoxic, has a history of usage as a phytopharmaceutical for brain edema associated with radiotherapy (a cancer treatment), and the general anti-inflammatory and anti-cancer effects make it a fairly interesting herb relative to others that have subpar evidence.

The anti-inflammatory and anti-cancer benefits appear to be dose-dependent, with the minimal dose that has been seen as effective being 3 doses of 400mg Boswellia Serrata (basic extract) taken daily with meals. If using Boswellia Serrata itself, doses can increase up to 1800mg taken thrice a day, but are usually in the range of 800-1200mg taken thrice a day.

If using the blends of 5-Loxin or Aflapin (concentrated sources of the main bioactive AKBA), oral doses of 100-250mg are taken once a day with a meal.

Preliminary evidence actually denotes that Boswellia’s AKBA can abolish some (but not all) tumors and their proliferation in rodents. Including pancreatic cancer, prostate cancer, and gliomas.

4.3. Neuroinflammation

A controlled study in mice where 1 hour of Ischmia (deprivation of oxygen) was followed by 24 hours of Reperfusion (resupply of oxygen coupled with oxidative damage) had intravenous Incensole Acetate administered at 1, 10, or 50mg/kg during Reperfusion found that the lesions in control were reduced by 22.3%, 57.8%, and 69.6% respectively.[51] Protection from neurological deficit induced by I/R injury followed a similar dose-dependent trend, and the mechanisms were thought to be secondary to anti-inflammation (with 50mg/kg reducing proinflammatory cytokines by 88% (TNF-?), 77% (IL-1?) and 80% (TGF-?) while suppressing nF-kB activity up to 84% at the highest dose and in a dose-dependent manner).[51] This protective effect was acute in nature, as starting intravenous application of Incensole Acetate 6 hours after reperfusion (rather than immediately) attenuated the reduction in infarct size form 77% to 37%.[51]

 

4.4. Edema

Boswellia Serrata gum was assigned the orphan drug status for the reduction of peritumoral edema by the European Medicines Agency (EMA) in 2002, where it goes by (in Europe) the name of H15.[52] A series of case studies in 12 persons with cerebral edema (7 glioblastoma, 2 anaplastic astrocytoma, two low-grade astrocytoma, and one with cerebral metastases from malignant melanoma) either off or on a stable dose of corticosteroids were given 1200mg H15 thrice a day (3600mg total) for 12 weeks was associated with reduced edema in 2/7 tumor bearers but benefitted all patients with edema due to radiotherapy.[52] Out of the 7 patients with tumors, no tumor responded to Boswellia and overall Boswellia was well tolerated.[52] Similar results have supposedly been found in a clinical trial mentioned in some studies,[53] where 30 patients with glioblastoma recieving 1200mg thrice daily Boswellia extract had less peritumoral edema accompanied with a general improvement of well being. The trial (Winking M et al; Boswellic acid as an inhibitor of the perifocal edema in malignant glioma in man. Neurooncology 1996) is not located online.

Appears to have limited but promising clinical effectiveness in reducing neural edema associated with radiotherapy

In a small unblinded study of 4 persons with chronic cluster headaches who also reported disturbed sleep (due to the headaches) given 350-700mg Boswellia Serrata thrice daily (1050-2100mg total) for up to 3 months noted resoluations in nocturnal headaches in all four subjects and an attenuation of overall headache severity and frequency.[54] It should be noted that cluster headaches have edema as a possible sign.[55]

Basically case studies (so not the most statistically sound), but shows promise for cluster headaches

 

4.5. Depression

A constituent of Boswellia known as Incensole (Acetate) appears to have anti-depressant effects in the Forced Swim Test in mice when injected with 50mg/kg acutely[8] and is effective at 10mg/kg in submissive mice.[12] Lower doses appear effective over time, with 1-5mg/kg in the submissive mice (10-50% acute dose) having similar effects after 1 week of ingestion.[12]

When 10mg/kg in submissive mice was compared to Paroxetine at 10mg/kg, it was technically not statistically different although underperformed,[12] while in normal mice given 50mg/kg it was less effective than 5mg/kg Diazepam in a Forced Swim Test.[8] Anti-depressant effects of Incensole Acetate may be mediated by TRPV3 receptors, as mice lacking these receptors do not have anti-depressant effects in response to injected Incensole.[8]

 

4.6. Anxiety

A constitient of Boswellia known as Incensole Acetate has failed to significantly influence anxiety at the same dose required to exert anti-depressive effects, 10mg/kg in submissive mice.[12] A reduction in anxiety has been seen at 50mg/kg in otherwise healthy mice as assessed by an elevated plus maze (with comparable effects to Diazepam).[8]

Anxiolytic effects of Incensole Acetate may be mediated by TRPV3 receptors, as mice lacking these receptors do not have anxiolytic effects in response to injected Incensole.[8]

 

4.7. Locomotion

A constitient of Boswellia known as Incensole Acetate has failed to significantly influence locotmotion at the same dose required to exert anti-depressive effects.[12] A reduction in locomotion has been noted in otherwise healthy mice given 50mg/kg Incensole.[8]

 

4.8. Cognition

One study using Boswellia papyrifera (similar assortment of bioactives, but may not apply to Serrata) as a 300mg/kg ethanolic extract orally thrice a day (900mg/kg total dose) for 4 weeks showed significant reductions in escape latency and travel distance in a water platform finding test; suggesting improved spatial memory formation.[56] These effects were also seen with isolated Boswellic Acids, and 300mg/kg Boswellic acids thrice a day (900mg/kg) was as effective at enhancing spatial memory formation as the active control of Nicotine (as tartrate salt; 1mcg infusion into the brain daily) although 100mg/kg thrice a day (300mg/kg) was also effective.[56]

 

5. Cardiovascular Health

 

5.1. Platelets

8 hours after consumption of 800mg Boswellia Serrata, there appears to be reduced collagen and arachidonic acid-induced blood clotting in otherwise healthy persons with no effect on Thrombin formation;[43] this was attributed to inhibition of cathepsin G,[41] but was deemed to be weak when compared to Naproxen.[43]

 

5.2. Immunology

Endothelial cells respond to TNF-? (a pro-inflammatory cytokine), and 22% of the genes influenced by TNF-? (n=552) are influenced by Boswellic Acids,[22] particularly those related to proteolysis, cell adhesion, and inflammation.[57] Three metalloproteins (MMP-3, 10, and 11) are potently suppressed in HMECs (endothelial cells) with incubation of Boswellic acids, with more potency being derived from a mixture with a higher concentration of 3-O-Acetyl-11-keto-?-Boswellic Acid (AKBA) where TNF-? induced MMP release was almost abolished.[22] These effects may underlie the protection seen with AKBA in ApoE-/- mice, where 100umol/kg injections of AKBA halved the size of lesions induced by LPS, a proinflammatory molecule[58] and to explain a reduction in TNF-? induced ICAM-1 secretion in vitro (ICAM-1 being an adhesion factor).[59] It should be noted that the direct sequestering of LPS applies to ?-Boswellic Acid and not AKBA, and cannot explain these observed results.[58]

The anti-inflammatory effects of AKBA may be cardioprotective by reducing inflammation and artherosclerosis; this has been seen in vivo after injections, but practical significant of oral ingestion is not known (AKBA tends to have low oral absorption)

 

6. Fat Mass and Obesity

 

6.1. Warmth

A component of Boswellia known as Incensole (Acetate) appears to actiate TRPV3, a receptor upon which activation induces the sensation of warmth;[8] this is a mechanism similar to Evodia rutaecarpa, and the sensation of warmth may create a false positive for fat loss (despite no energy being expended to produce heat, but merely a sensory change).

Warmth from Boswellia Serrata (currently not demonstrated to be an effect) may be a false positive for fat loss due to having the ability to act on a receptor class that induces the sensation of warmth independent of fat burning

 

7. Skeleton and Bone Health

 

7.1. Osteoclasts

A protein known as RANKL is able to induce osteoclastogenesis via activating nF-kB[60][61] and boswellia serrata (via AKBA) can suppress RANKL-induced osteclastogenesis secondary to nF-kB inhibition at a concentration as low as 300nM (75% inhibition in vitro); AKBA also prevented TNF-? from activating nF-kB (3?M).[24] It does not appear to directly interfere with the TNF-? induced nF-kB complexation, but interferes with the genomic transcription of nF-kB.[24]

Boswellia serrata (via nF-kB inhibition from AKBA) appears to hinder the proliferation of osteoclasts

 

7.2. Mechanisms

In human chondrocytes (joint cells), Boswellia with 30% AKBA is able to suppress the TNF-? induced release of MMP-3 with an IC50 of 31.71ug/mL;[59] thought to be relevant to osteoarthritis pathology.

 

7.3. Osteoarthritis

Boswellia Serrata is thought to aid the pathology of Osteoarthritis due to being involved in a herbal combination therapy alongside Ashwagandha and Curcuma Longa (source of Curcumin);[62] the same mixture of herbs which has failed to show any benefit to Rheumatoid arthritis.[63]

In a study comparing two treatments against placebo, the first treatment under the brand name of 5-Loxin (100mg of Boswellia Serrata standardized to 30mg AKBA) was compared to another formulation of Boswellia (Aflapin at 100mg) in 60 persons with confirmed osteoarthritis;[59] the results over 90 days suggested that 5-Loxin reduced symptoms of osteroarthritis on several rating scales by 31.6% (Visual Analogue Scale), 30.3% (WOMAC; pain subset), 42.2% (WOMAC; stiffness subset), 21.25% (WOMAC; functionality subset), and 18.35% (Lequesne’s Functional Index) although the Aflapin group outperformed on all parameters. Both groups reported statistically significant improvements within a week of treatment (around 8% reduction with 5-Loxin)[59] with another study noting improvements by day 5 on VAS and LFI rating scales but not WOMAC[64] and a third study suggesting that the improvements within a week occur with higher (250mg) dose of 5-Loxin and take longer with lower (100mg) doses.[65] Overall magnitude of benefits in other studies are improved symptoms of osteoarthritis as assessed by VAS (37.6%), LFI (32%), and WOMAC subsets of pain (40.1%) stiffness (41.3%) and function (38.8%) after 30 days of 100mg Aflapin[64] and reductions in VAS (48.83-65.94%), LFI (23.79-31.34%), WOMAC pain ( 39.61-52.05%) function (49.34%) and stiffness (62.22%) over 90 days of either 100mg or 250mg of 5-Loxin; with the more significant improvements associated with the higher oral dose and both the function ( 28.62%) and stiffness (42.5%) with the low dose failing to be statistically significant.[65]

Currently a multitude of well controlled studies with either 5-Loxin or Aflapin (nutraceutical patents of Boswellia Serrata with concentrated AKBA to 30% and 20%, respectively), but all the studies using these formulations procured external funding from the producer of the supplements. It did not appear to have any influence on the results and seem to have been conducted indpendently.

Another study of persons with osteoarthritis noted that 6g of basic plant extract in three doses of 2g alongside meals was able to reduce knee pain 70.96-73.68%, shoulder pain by 83.33%, and absolved spinal pain from baseline; improvements occurred in swelling and joint mobility to similar degrees and improvements were noted in happiness and activity levels secondary to reduced pain.[66] Conclusions from this study are limited due to being unblinded and without control group,[66] and despite the promise of the above studies in potency there may not be sufficient independent evidence for Boswellia Serrata for attenuating general joint pain.[67][68]

Definitely shows a large degree of promise in treating joint pain without adverse effects, but the amount of interventions on the matter are enough to show this promise but not enough to draw conclusive statements on its efficacy for treating joint pain; a highly promising but not fully established nutraceutical

 

8. Inflammation and Immunology

 

8.1. Mechanisms (Enzymatic)

5-Lipoxygenase (5-LOX) is an enzyme that used Arachidonic Acid (omega-6 fatty acid) as a substrate to create pro-inflammatory cytokines such as 5-hydroxyeicosatetraenoic acid (5-HETE) and Leukotriene B4; this 5-LOX/Leukotriene pathway being a pro-inflammatory signalling pathway in the body.[69] 11-keto-?-boswellic acid and 3-O-Acetyl-11-keto-?-boswellic acid are inhibitors of 5-LOX with IC50 values of 2.8uM and 1.5uM respectively,[70][71] and although other Boswellic acids (such as ?-boswellic acid) can inhibit the enzyme partially the 11-keto group appears to enhance potency.[71] The inhibitory potential of Boswellic Acids on 5-LOX is nonredox in nature.[72] Due to the inhibitory potential of these two Boswellic acids in particular on 5-LOX, the 11-keto Boswellic acids are thought to be the most important.

However, serum binding of AKBA to albumin is very high (greater than 95%), and 800mg of Boswellia given to participants failed to influence plasma Leukotriene B4 levels (which should be reduced with oral intake of 5-LOX inhibitors);[44] whether this can be overcome with higher doses traditionally used in interventions is not known.

Boswellic Acids do not appear to greatly inhibit 12-LOX nor Cyclooxygenase (COX) enzymes in vitro, nor do they prevent peroxidation of Arachidonic acid induced by iron or ascorbate.[73][74] One study using platelets, however, did note inhibition on COX1 and 12LOX by 3-O-acetyl-11-keto-?-Boswellic Acid (AKBA) with an IC50 of 6uM in platelets and 32uM in a cell-free assay;[75] with another author suggesting that their unpublished data is in accordance.[76]

The most well known mechanism of action of Boswellia appears to he 5-Lipoxygenase inhibition, and the two most potent bioactives in this regard appear to be the 11-keto Boswellic acids. The 5-LOX inhibition is direct and specific, rather than a general inhibition that can be induced by anti-oxidant compounds; however, whether this mechanism is active in vivo is currently under investigation (with one report suggesting it is unlikely)

No significant interactions with the two Cyclooxygenase enzymes (COX1 and COX2), the targets of NSAID drugs, although some inhibition of COX1 may be possible

Other antiinflammatory mechanisms of Boswellic acid include nF-kB inhibition,[77] which has been noted in vivo in mice given the boswellic acid AKBA in 100umol/kg injections[58][78] and appears to be mediated by multiple mechanisms. In response to Tumor-Necrosis Factor alpha (TNF-?), AKBA appears to bind directly to IKKs and prevent activation of I?B? and p65 (which then prevents induction of nF-kB)[79] and may also directly bind to Lipopolysaccharide (LPS; a bacterial toxin that induces nF-kB).[80] ?-Boswellic acid was able to sequester LPS with an IC50 of 1.8uM, which underperformed the active control of polymyxin B which wholly sequestered LPS at 100nM.[80][81] This appears to be a main mechanism of anti-inflammation, as the reduction of iNOS induction seen in macrophages is wholly due to binding to LPS (with Boswellic acids that do not bind to LPS, such as AKBA, being ineffective).[80] Both studies noted that nF-kB translocation induced by interferons (IFN-?) was unaffected by Boswellic acids.[79][80]

Incensole Acetate in Boswellia species may also inhibit nF-kB activation, as Incensole can inhibit IKK activation loop phosphorylation induced by TAK/TAB and has no inhibitory effect in T-Cells.[82]

General inhibitory effects on nF-kB, a locus for inflammation in response to antigens and dietary stressors; Incensole seems to have novel mechanisms of action, and ?-Boswellic acid appears to bind directly to LPS

Cathepsin G (CatG) inhibition, with ?-Boswellic acid having an IC50 of 0.8umol/L.[41] Cathepsin inhibition is a therapeutic target for antiinflammatory actions in neutrophils (immune cells).[83] AKBA may also be relevant for CatG inhibition as it has an IC50 of 1.2umol/L

Microsomal prostaglandin E2 synthase inhibition has been noted with Boswellic acids,[84] where the IC50 value for ?-Boswellic acid is 5umol/L and the 11-keto Boswellic acids (‘main’ two) appear to be relatively inert following injections into rats.[84] MPE2S inhibition is an antiinflammatory therapeutic target.[85] Additionally, a lupeolic acid (a minor class of compounds in Boswellia Serrata) appears to inhibit Phospholipase A(2) with an IC50 range of 2.3-6.9uM in general and cytoplasmic PLA(2)? at 3.6uM; this inhibits formation of Arachidonic Acid prior to subsequent metabolism by 5-LOX, 12-LOX, or COX-1.[86]

Human Leukocyte Elastase (HLE) is also inhibited by Boswellic acids.[87] HLE is an enzyme released by immune cells (PMNs) and 3-O-Acetyl-11-keto-?-Boswellic acid inhibits HLE with an IC50 of 15?M (7.5ug/mL has also been reported[76]), and in this same study they noted some inhibition with both ?-boswellic acid and Ursolic Acid, but an apparent lack of effect of the structurally related compound 18-?-glycyrrhetinic acid (from Licorice).[87] No other compound in this assay inhibited 5-Lipoxygenase.

Several other direct anti-inflammatory mechanisms exist that are within the physiological ranges observed in pharmacokinetic studies, suggesting that they may be relevant to the actions of Boswellia

 

8.2. Innate Immunity

?-boswellic acid and ?-boswellic acid have been noted to inhibit the guinea pig complement system at 5-100uM (Wagner et al. 1987 in German; cited vicariously through[76]) and have been replicated elsewhere,[88] and this was thought to be secondary to inhibiting C3-convertase in vitro.[88]

 

8.3. Adaptive Immunity (B-Cells and Antibodies)

In a test in mice given sheep erythrocytes (to stimulate humoral immunity), a single dose of 50-200mg/kg Boswellic acids (mixed) induced a dose-dependent reduction of primary hemagglutinating antibody titres when measured 4 days after simultaneous administration of Boswellic acids and the antigen by 10.4–32.8%,[89] Azathioprine at 200mg/kg as an active control reduced hemagglutinating antibody titres by 10.4%.[76]

However, when oral dosing of Boswellic acids were given for 5 days preceding and following exposure to the antigen antibody production was increased by 15.38–26.92% at oral doses of 25-200mg/kg Boswellic acids (with most potency at the lowest dose).[89] This same dose range produced a 37.93–63.79% increase in the primary humoral response when preloaded for 7 days, while the active control of Levamisole (2.5mg/kg) increased the primary response by 25%.[89]

Increased antibody synthesis has also been noted with the polysaccharide fragment in both primary (83.8%) and secondary (79.3%) titres in response to oral ingestion of 10mg/kg polysaccharide, which was more potent than the active control of 2.5mg/kg Levamisole (which was comparable in potency to 1-3mg/kg polysaccharide) over 7-15 days of treatment.[20]

May enhance immunity (antibody response to antigens, or adaptive immunity in response to infection) but this may require constant loading rather than acute loading. A single dose may actually be immunosuppressive

One study conducted in mice given an antigen (hepatitis B surface antigen) using BOS2000 (polysaccharides) as an adjunvant alongside vaccination noted that BOS2000 was able to dose dependently increase the IgA response to the antigen, with 10mcg/mL outperforming 0.5mg/mL aluminum (active control) and doses up to 80mcg increasing the response further.[90]

May augment vaccine efficacy, but no oral studies have been conducted

 

8.4. Lymphocytes

It has previously been noted that in non-immunized mice with no antigen, Boswellic acids have no cumulative effect on Lymphocyte proliferation at 1.95-125ug/mL while acute incubation with Boswellic acids and mitogen stimulating factors (PHA, LPS, Alloantigen, and Concanavalin A) suppress proliferation of lymphocytes.[89] This is in contrast to a study conducted with Boswellia cartenii in heparanized venous blood from participants where acute incubation of different extracts with mitogens (PHA) suggested that T-cell transformation was enhanced with the ethanolic extract (containing Boswellic acids common to both species).[91] This study noted that that TC50 value (concentration of bioactive converting half of lymphocytes to active T-cells) ?-boswellic acid, Acetyl-?-boswellic acid, and Acetyl-?-Boswellic acid were 0.0022uM, 0.005uM, and 0.0029uM respectively. Other compounds that appeared to be active were Lupeol (0.0029uM) and 3-oxo-tirucallic acid (0.011uM) while 1mg/mL of the alcoholic extract overall had a TC50 of 0.55mg/mL and induced 90% conversion at 1mg/mL.[91] These effects were reported to be comparable to Echinacea Purpurea.

Stimulation has been noted with the polysaccharide fragment in response to mitogens at 1, 3, and 10mg/kg with maximal effectiveness at 3mg/kg.[20] This same study noted a proliferation of both CD4 and CD8 positive lymphocytes.[20]

Mixed results in regards to lymphocyte proliferation, but appears to stimulate proliferation (pro-immunity result)

 

8.5. Macrophages

Activation of Macrophages by LPS (may only hold biological relevance when it comes to gut-immunity relations, as LPS is unique to bacteria) can be abolished with direct binding between ?-Boswellic acid and LPS.[80]

Otherwise, phagocytosis of macrophages is enhanced when Boswellic acids are incubated with the macrophages at concentrations of 1.95–125?g/mL, with maximal efficacy at 62.25?g/mL.[89] Enhancement of phagocytosis is also noted in vivo after oral adminsitration of low doses of the polysaccharide component BOS 2000 where 1, 3, and 10mg/kg increased phagocytosis [20] Relative to the active control of 2.5mg/kg Levamisole, 1mg/kg was similarly effective while 3mg/kg was more effective and 10mg/kg outperforming all other groups.[20]

 

8.6. Pancreatic

In a rodent model of toxin-induced Type 1 diabetes (multiple low dose streptozotocin at 40mg/kg), injections of 150mg/kg Boswellia Serrata (5.48% and 4.66% KBA and AKBA) failed to influence blood glucose in otherwise normal mice yet outright abolished the increase of blood glucose in response to the toxin when both were administered fro 5-10 days and measured over 25 subsequent days.[92] Histology between control and the Boswellia group did not appear significantly different from each other, and the serum increase in granulocyte-colony stimulating factor was normalized (with a significant attenuation of GM-CSF) while the levels of IL-1A, IL-1?, and TNF-? were equal between control and Boswellia (attenuation of IL-2, IL-6, and IFN-? that was not equal to control but lesser than disease control group).[92]

Anti-inflammatory effects have potent protective effects against streptozotocin-induced toxic effects to the pancreas, with this rat study literally negating most of the toxic effects of streptozotocin

Read this whole article.

San Leng – Sparganium rhizome (or Scirpus) – “Three Edges”

Nature: bitter, acrid, neutral

Enters: Liver, Spleen

Actions: Strongly promotes blood and Qi circulation, and dispels blood stasis; relieves pain; dissolves accumulations.

Indications:
• Blood stasis: amenorrhea with abdominal pain, post-partum abdominal pain, abdominal masses, dysmenorrhea.
• Food retention and stagnant Qi: (severe) distending pain in the epigastrium and abdomen.
• Often combined with E zhu. Liu says San leng is stronger than E Zhu at promoting Qi circulation, but weaker than E zhu at promoting blood circulation. Bensky/Gamble says just the opposite.
• Used with E zhu in oncology (useful in hepatic carcinoma in one study).
• Kamto: San leng + E zhu is great combination for depression.
HF: An important herb in anti-Gu therapy to move Qi (xing Qi) and break accumulation (po ji).
DY: With E zhu to strongly and effectively break both the Qi and blood, regulate and rectify the Qi and blood, stop pain, and reduce food accumulation. For specific indications and notes on this combination, see E zhu in this category.

Dose: 3-9g

Shui Zhi – Leech – Hirudo

Nature: bitter, salty, slightly toxic, neutral

Enters: Liver, Bladder

Actions: Strongly dispels blood stasis; reduces immobile masses.

Indications:
• Blood stasis: amenorrhea, traumatic injury, masses.
• Wind-stroke.
• Hypercholesterolemia.
• Coronary heart disease.
Shui zhi eyedrops are very effective for acute conjunctivitis. (May cause transitory pain upon application, but no other side effects.)
• Hirudin (a component): anticoagulant (especially in ethanol extract) – is denatured by heat. Therefore, the herb should not be cooked long, if at all. Leech extracts (hirudin) are tremendously popular in Chinese hospitals, used for everything Warfarin (Coumadin) is prescribed for.
• Leech secretes a histamine-like substance that acts as a vasodilator.
• Contraindicated in pregnancy.
• Some say the herb should be toasted until yellow, then powdered and taken directly.
• Guohui Liu says: Much stronger than Tu bie chong. Bensky/Gamble say: More moderate than Tu bie chong but with a more sustained effect.
MLT: Hirudin interferes with the clotting effect of thrombin on fibrinogen.

Dose: 1.5-6g

Si Gua Luo – Luffa – Dried skeleton of vegetable sponge – “Net of String Melon”

Nature: sweet, neutral

Enters: Liver, Lung, Stomach

Actions: Expels wind; invigorates the channels; expels phlegm; expels summer-heat; promotes urination; benefits the breasts.

Indications:
• Damp-heat obstruction of the channels and muscles: chest and flank soreness, pain and soreness in the muscles and sinews, stiffness in the joints. Also for traumatic injury.
• Lung heat: cough with high fever, chest pain, and sputum that is difficult to expectorate.
• Summer-heat: fever, scanty urine.
• Swollen, painful breasts; insufficient lactation; breast abscess.
• Antitussive and expectorant (though not as strong as the vine if the same plant).
• Doctrine of signatures: its affinity for the muscles and sinews is reflected in its sinewy, fibrous makeup.

Dose: 6-12g (up to 30g when used alone)

Su Mu – Sappan wood – Caesalpinia sappan

Nature: sweet, salty, slightly acrid, neutral

Enters: Liver, Heart, Spleen

Actions: Promotes blood circulation; dispels blood stasis from the channels; relieves pain; reduces swelling; stops bleeding.

Indications:
• Blood stasis: amenorrhea, abdominal pain after childbirth, pain and swelling of traumatic injury – falls, fractures, contusions, sprains.
• Excessive post-partum bleeding with dizziness, vertigo, and shortness of breath.
• Similar to Hong hua but not often used – usually for fractures and sprains.
• Antibiotic: particularly against staph, salmonella.
• Contraindicated in pregnancy.
Hsu: Analgesic; inhibitory effect on the CNS; tranquilizer – a small dose can induce sleep; shortens blood coagulation time.

Dose: 3-10g

Tao Ren – Peach kernel – Prunus persica (or P. davidiana)

Nature: bitter, neutral

Enters: Liver, Heart, Large Intestine, Lung

Actions: Promotes blood circulation, dispels blood stasis; moistens the large intestine, promotes bowel movement; unblocks the menses.

Indications:
• Blood stasis: dysmenorrhea, abdominal pain after childbirth, traumatic injury, flank pain, Lung abscess, intestinal abscess with immobile abdominal mass.
• Large intestine dryness: constipation.
• Alcohol extractions have a weak anticoagulant effect.
• Traditionally this herb is used with its peel. To promote bowel movement, remove the tip.
• Contraindicated in pregnancy.
• Sometimes double kernels occur (they look like “Siamese twin” kernels) – these are said to be toxic.
Hsu: Anticoagulant, antiphlogistic, detoxicant, laxative.
DY: Tends to dispel blood stasis in the lower part of the body, in the abdomen, and in the organs; very slightly nourishes blood.
• Like Xing ren, Tao ren is slightly toxic. The toxicity is localized in the superficial skin and the tip of the seed. The preparation, scalded Tao ren, eliminates this toxicity. However, in this form, Tao ren is less powerful at quickening the blood and dispelling stasis.
• With Hong hua: Hong hua is stronger than Tao ren at moving blood, while Tao ren is stronger at dispelling stasis. Together, they complement and reinforce each other to effectively quicken the blood, dispel stasis, engender blood, and stop pain. For specific indications and notes on this combination, see Hong hua in this category.

Dose: 4.5-10g

Tu Bie Chong (Di Bie Chong, Zhe Chong) – Eupolyphaga – Wingless Cockroach – “Land Soft-Shelled Turtle”

Nature: salty, slightly toxic, cold

Enters: Liver, Heart, Stomach

Actions: Strongly dispels blood stasis; promotes regeneration of tendons and bones.

Indications:
• Blood stasis: amenorrhea, abdominal pain after childbirth, masses, numb and swollen tongue.
• Sprains, fractures, contusions, lacerations.
• Acute lumbar strain: toast, grind and take as a powder (1-1.5g).
• Coronary artery disease
• For numb and swollen tongue, grind 6g herb with 3g table salt and apply directly.
• Usually ground and put into a tea bag (will float otherwise).
• Soak in wine and then dry-fry to enhance the herb’s effect.
• Contraindicated in pregnancy.
• Liu: Weaker than Shui zhi. Bensky/Gamble: More intense but shorter-acting than Shui zhi. Tu bie chong is used more for treating channel-level problems. The two herbs are often used together.
• Kamto: Ideal for stroke ““ guides to brain. (This is the large, winged cockroach actually)
HF: For cancer: (doctrine of signatures) cockroaches go where the nastiest stuff is and eat it.

Dose: 3-6g

Wang Bu Liu Xing – Vaccaria seed – (Ficus pumila, Hypericum sampsoni, and Vicia sativa also used as substitutes, each with unique properties) – “King Who Does Not Stay But Departs”

Nature: bitter, neutral

Enters: Liver, Stomach

Actions: Promotes blood circulation, invigorates the channels; dispels blood stasis; reduces swelling; promotes lactation; unblocks menstruation; slightly promotes urination.

Indications:
• Blood stasis: dysmenorrhea, amenorrhea; galactostasis after childbirth, mastitis.
• Swellings: benign prostatic hypertrophy/prostatitis, testes, breasts.
• Topical: herpes zoster (shingles) – use a paste of the toasted, powdered seeds mixed with sesame oil. Apply locally once or twice a day and leave on for (at least) 30 minutes. Avoid open sores.
• Used as ear seeds, particularly for the treatment of gall stones.
• Stimulates the uterus.
• Pound before decocting or fry until it pops like popcorn.

Dose: 3-30g

Wu Ling Zhi – Flying Squirrel feces (Pteromys or Trogopterus) – “Fat of the Five Spirits”

Nature: bitter, sweet, warm

Enters: Liver, Spleen

Actions: Promotes blood circulation; relieves pain; dispels blood stasis; stops bleeding.

Indications:
• Blood stasis: pain – dysmenorrhea, abdominal pain after childbirth, chest, epigastric, or abdominal pain; lochioschesis, amenorrhea, uterine bleeding.
• Childhood nutritional impairment with focal distention.
• Often combined with Pu huang in Shi Xiao San for pain (usually dysmenorrhea with bleeding).
• Dry fry the herb to stop bleeding.
• Vinegar fry it to enhance its blood circulating properties.
• Often decocted in cheesecloth or a tea bag.
• Bat (Pteropus) feces is sometimes used as this herb.
CHA: Heiko Lade, 3-19-01: No one in China has used the correct Wu ling zhi for about 20 years because the habitats where flying squirrels used to live are virtually non-existent now, and it is almost an extinct species. Instead they use the feces of a wild field rat.
MLT: For fibroids, uterine or ovarian cysts, tumors.
Hsu: Analgesic – relaxes spasm of smooth muscle; antibacterial (tuberculosis), antifungal.

Dose: 3-10g

Yan Hu Suo – Corydalis rhizome

Nature: acrid, bitter, warm

Enters: Heart, Liver, Spleen, Stomach, Lung

Actions: Promotes blood and Qi circulation, relieves pain.

Indications:
• Blood and Qi stagnation: pain – chest, abdomen, epigastrium, limbs, hernial, trauma, and especially dysmenorrhea. This is the premier analgesic herb.
• Can be used for any kind of pain when combined appropriately.
• Treats ulcers.
• Possesses 1% the analgesic strength of opium.
• Some hypnotic effects; used to promote sleep for insomnia.
• Toast or fry in vinegar to enhance its blood circulating properties.
• Use as a powder for a stronger effect.
Jin: Focuses on the liver.
RW: Greatly reduces the tremors of Parkinson’s disease, chorea minor, and other forms of ataxia.
NAH: Contains the alkaloid bulbocapriine, which has been used for Parkinson’s, Meniere’s, convulsions.
Hsu: Tranquilizer, analgesic, spasmolytic, anti-ulcerative agent.
DY: When used alone or with small amounts of other herbs, use up to 50g in decoction or 10g directly as powder.
• Stops pain in the whole body – the upper and lower, interior and exterior.
• A medicinal for the qi within the blood. It moves the Yang aspect of the blood. It disperses Qi stagnation in the blood and blood stagnation in the Qi. It is, therefore, a medicinal which quickens simultaneously the Qi and blood, but which, nevertheless, has more of its action on the blood than the Qi.
• With Chuan lian zi to clear heat, eliminate dampness, course the liver, move the Qi and blood, and stop pain. This combination (Jin Ling Zi San) is used for indications such as:
– 1. Pain in the chest, epigastrium, abdomen, and lateral costal regions due to liver depression Qi stagnation sometimes associated with liver blood stasis. (Use wine mix-fried Yan hu suo and scorched Chuan lian zi.)
– 2. Liver depression Qi stagnation transforming into liver heat or fire.
– 3. Dysmenorrhea and menstrual irregularities due to Qi and/or blood stasis. (Use scorched Chuan lian zi and vinegar mix-fried Yan hu suo.)
– 4. Heart pain due to Qi and blood stagnation. (Use wine mix-fried Yan hu suo and scorched Chuan lian zi.)
– 5. Inguinal hernia or diseases of the scrotum or testicles due to Qi stagnating in the liver channel. (Use scorched Chuan lian zi and vinegar mix-fried Yan hu suo.)
– 6. Hepatitis, cholecystitis, and angiocholitis due to damp-heat in the liver and gallbladder. (Use scorched Chuan lian zi and vinegar mix-fried Yan hu suo.)
– This combination is a major analgesic which can be added to other prescriptions when pain is a key manifestation of the disorder and especially if this pain is due to Qi stagnation and blood stasis. If there is a headache, add Chuan xiong and Hong hua. If there is chest pain, add Jie geng, Zhi ke, and Xie bai. If there is lateral costal pain, add Chai hu and Yu jin. If there is stomach and epigastric pain, add Mu xiang and Dan shen. If there is lower abdominal pain, add Mu xiang and Tao ren. If there is lower abdomen pain occurring on both sides of the abdomen in the area traversed by the liver channel, add Wu yao and Xiao hui xiang.

Dose: 4.5-12g

Yi Mu Cao – Leonurus – Chinese Motherwort – “Benefit Mother Herb”

Nature: acrid, bitter, slightly cold

Enters: Heart, Liver, Bladder

Actions: Promotes blood circulation, dispels blood stasis; regulates the menses; reduces masses; promotes urination, relieves swelling and edema.

Indications:
• Blood stasis: irregular menstruation, slow flow, amenorrhea with lower abdominal pain, lochioschesis and abdominal pain after childbirth, infertility, immobile abdominal masses, premenstrual abdominal pain.
• Edema with scanty urination, especially with hematuria.
• Acute systemic edema, especially when accompanied by hematuria.
• Damp-heat in the lower Jiao.
• Benign prostatic hypertrophy, prostate cancer, testicular pain.
• Contracts the uterus.
• Opens the coronary artery, treats coronary artery disease.
• Lowers blood pressure.
• Generally contraindicated in pregnancy.
MLT: Also for acute and chronic nephritis; postpartum uterine bleeding; incomplete involution of uterus; myocardial infarction: increases circulation to the coronary artery, lowers heart rate, improves microcirculation, prevents platelet agglutination.
• Cook 27g Yi mu cao with 9g Dang gui and take in 3 doses to help restore the womb after childbirth.
K&R: (L. cardiaca) Cardiotonic; stimulates oxytocin; antispasmodic; mild diuretic.
• Fire yin.
• Precordial pain, palpitations, cardiopathy, heart disease.
• Amenorrhea, dysmenorrhea; contracts and clears the uterus postpartum.
• PID – improves circulation in the lower abdomen.
• Relieves edema from nephritis; hematuria from renal calculi.
• Insomnia; goiter; epilepsy.
• Recent use in China as a morning-after contraceptive.
• Lowers blood viscosity and platelet aggregation rate.
• The extract is used for headache, insomnia, vertigo, peripheral circulatory paresthesias.
JC: (L. cardiaca) Emmenagogue, heart tonic, diaphoretic, tonic, nervine, antispasmodic, aperient, hepatic, diuretic.
• May be the best heart tonic known. Calms and supports the heart and nerves, may be used in large doses. Beneficial as a healing tonic in recovering from debilitating fever where other tonics are inadmissible.
• Chest cold, cramps, pains: foment over affected area and take internally.
• Delayed menstruation: give the syrup in hot water. When normal flow is re-established, take cold as a tonic.
• Influenza, severe colds, low fevers: give as hot as can be taken until the patient perspires freely.
• Acute and chronic heart problems (palpitations, endocarditis, pericarditis, intermittent pulse, etc.), epilepsy, nervous exhaustion, spasms, twitching, chorea, neuralgia, spinal disease, indigestion, liver affections, vaginitis (douche).
PCBDP: Chinese studies show anti-platelet aggregation action, lowers blood lipids, inhibitory effects on pulsating myocardial cells.
RW: (L. cardiaca) Antithyroid: for hyperthyroidism, palpitations, tachycardia.
MW: (L. cardiaca) Doctrine of signatures: has “goose tongue” leaves – a signature for rhythm – for the heart – palpitations.
• Also a good spinal remedy – for spinal irritation.
Hsu: Stimulates the uterus, increases flexibility and tonicity of uterus (much weaker than pituitary hormones); diuretic; hypotensive; antibacterial.
DY: Slightly nourishes blood – just enough to not damage the blood when used to dispel stasis.
• Must be used in relatively high dosage (15-30 or more).

Dose: 9-60g (to 120g for edema in glomerulonephritis)

 
Chong Wei Zi: the seed
• Sweet, slightly cold.
• Dispels blood stasis, but is also astringent and tonic; cools the liver; brightens the eyes.
• For excessive menstruation/uterine bleeding.
• Liver heat: for red, painful, swollen eyes, pterygium.

Dose: 3-9g

Yu Jin – Curcuma tuber (Curcuma aromatica, but sometimes: C. longa, C. kwangsinensis, C. zedoaria) – “Constrained Metal”

Nature: acrid, bitter, cold

Enters: Heart, Liver, Gallbladder, Lung

Actions: Promotes blood and Qi circulation, dispels blood stasis; promotes circulation of liver Qi; relieves pain; clears heart heat; cools the blood; opens the orifices of the heart; normalizes the function of the gallbladder and relieves jaundice.

Indications:
• Qi or blood stasis which has created heat.
• Liver Qi stagnation and blood stasis: pain in the chest, hypochondria, costal region, and abdomen, irregular menstruation, dysmenorrhea, masses in the abdomen.
• Blockage of the heart by damp-heat: distention in the chest and epigastrium, fuzzy head.
• Blockage of heart by stagnant phlegm and Qi: seizures, mania, mental depression, anxiety, agitation.
• Liver Qi stagnation heat: hematemesis, hematuria, epistaxis during menstrual period.
• Gallbladder disorders: damp-heat, jaundice, gall stones, hepatitis.
• Lung heat.
• Topical and internal: pain related to traumatic injury, chronic sores.
• Viral hepatitis: effective at alleviating pain, treating jaundice, and reducing organomegaly.
• There are two main types of Yu jin: Chuan yu jin (“River Constrained Gold”) is less commonly used, is considered to be milder, and is usually used for patients who are relatively weak; Guang yu jin (“Broad Constrained Gold”) is the more commonly used variety.
• There has been much confusion in the identification of Yu jin vs Jiang huang, and even another Curcuma species, E zhu. Subhuti Dharmananda explains the taxonomy and history in this article.
MLT: Use with Shi chang pu for mental derangement, the effects of intoxicating drugs such as marijuana, and lack of focus.
Hsu: Promotes production and secretion of bile; stimulates motor activities of the stomach; stimulates gastric secretions and appetite.
HF: A Sha Chong (kill worms or parasites) herb, important in Gu Zheng (Gu parasites) formulas.

Dose: 4.5-9g

Yue Ji Hua – Partially-opened Chinese Tea Rose – Rosa chinensis – “Moon Season Flower”

Nature: sweet, warm

Enters: Liver

Actions: Promotes blood circulation; regulates menstruation; reduces swelling.

Indications:
• Blood stasis: scanty menstruation, amenorrhea, chest pain, abdominal pain and distention.
• Swelling: neck swellings, scrofula.
• With brown sugar: for amenorrhea or scanty menstruation with abdominal pain, emotional stress, and constipation.
Dose: 3-6g

Zang Hong Hua – Xi Hong Hua – Saffron – Crocus sativa stigma

• Similar to Hong hua but much stronger and much more expensive.
• It is used in relatively severe cases, mainly for painful obstruction of the chest.
• Used for depression. Extensive research in Iran (main global producer) looks very promising.
• Topical for acne.
• Regulates menstruation.
• Eases cough and asthmatic breathing.
• Reduces fever and inflammation.
• Not to be confused with Meadow Saffron (Colchicum autumnale) which is toxic.

Dose: 1-3g in decoction or 0.5-1.5g eaten directly

Ze Lan – Lycopus – Bugleweed – “Marsh Orchid”

Nature: acrid, bitter, slightly warm

Enters: Liver, Spleen

Actions: Promotes blood circulation (without damaging Zhen Qi), dispels blood stasis; promotes urination, relieves edema; frees the flow of liver Qi; opens the channels; unblocks the menses.

Indications:
• Blood stasis: irregular menstruation, dysmenorrhea, amenorrhea, abdominal pain during menses and after childbirth, masses in the abdomen, traumatic injury, abscess, pain and swelling, pain in the chest and hypochondria, carbuncles.
• Edema over the face and body, dysuria, particularly post partum.
• Postpartum painful urinary dysfunction.
• Cardiotonic effect.
• Also for prostatitis/benign prostatic hypertrophy.
• Topical: for pain and swelling, traumatic injury, abscesses.
• Very safe herb.
• In some parts of China, Pei lan (Eupatorium) is sometimes used as this herb. (Pei lan does not promote blood circulation.)
HF: An important herb in anti-Gu therapy to move Qi (xing Qi) and break accumulation (po ji).
K&R: Thyroid inhibitor, pituitary inhibitor (TSH, gonadotropins, prolactin), sympatholytic. Fire yang.
• Tachycardia and arrhythmia especially with hyperthyroidism.
• Hormonal influence to treat various prostate and ovary disorders.
RW: Antithyroid: for milder hyperthyroidism: small doses, takes 3-4 weeks for good effect (mainly helps palpitations). Use with Leonurus.

Dose: 3-15g (up to 30g topically)

Zi Ran Tong – Iron Pyrite (An Iron Sulfide)

Nature: acrid, neutral

Enters: Liver, Kidney

Actions: Dispels blood stasis, relieves pain; promotes regeneration of bones and sinews.

Indications:
• Blood and Qi stasis caused by injury: swelling, pain, and especially fractures.
• Has been used successfully for endemic goiter.
• Decoct for at least 30 minutes or take directly as powder.
• Major known constituents include: ferrous disulfide, copper, nickel, arsenic. Due to arsenic content, probably toxic.

Dose: 3-15g (0.3-0.6g directly as powder)