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.
• 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.
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.
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. 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). 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%.
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. 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. Out of the 7 patients with tumors, no tumor responded to Boswellia and overall Boswellia was well tolerated. Similar results have supposedly been found in a clinical trial mentioned in some studies, 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. It should be noted that cluster headaches have edema as a possible sign.
Basically case studies (so not the most statistically sound), but shows promise for cluster headaches
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 and is effective at 10mg/kg in submissive mice. 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.
When 10mg/kg in submissive mice was compared to Paroxetine at 10mg/kg, it was technically not statistically different although underperformed, while in normal mice given 50mg/kg it was less effective than 5mg/kg Diazepam in a Forced Swim Test. 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.
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. 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).
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.
A constitient of Boswellia known as Incensole Acetate has failed to significantly influence locotmotion at the same dose required to exert anti-depressive effects. A reduction in locomotion has been noted in otherwise healthy mice given 50mg/kg Incensole.
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. 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.
5. Cardiovascular Health
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; this was attributed to inhibition of cathepsin G, but was deemed to be weak when compared to Naproxen.
Endothelial cells respond to TNF-? (a pro-inflammatory cytokine), and 22% of the genes influenced by TNF-? (n=552) are influenced by Boswellic Acids, particularly those related to proteolysis, cell adhesion, and inflammation. 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. 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 and to explain a reduction in TNF-? induced ICAM-1 secretion in vitro (ICAM-1 being an adhesion factor). It should be noted that the direct sequestering of LPS applies to ?-Boswellic Acid and not AKBA, and cannot explain these observed results.
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
A component of Boswellia known as Incensole (Acetate) appears to actiate TRPV3, a receptor upon which activation induces the sensation of warmth; 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
A protein known as RANKL is able to induce osteoclastogenesis via activating nF-kB 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). It does not appear to directly interfere with the TNF-? induced nF-kB complexation, but interferes with the genomic transcription of nF-kB.
Boswellia serrata (via nF-kB inhibition from AKBA) appears to hinder the proliferation of osteoclasts
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; thought to be relevant to osteoarthritis pathology.
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); the same mixture of herbs which has failed to show any benefit to Rheumatoid arthritis.
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; 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) with another study noting improvements by day 5 on VAS and LFI rating scales but not WOMAC 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. 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 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.
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. Conclusions from this study are limited due to being unblinded and without control group, 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.
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. 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, and although other Boswellic acids (such as ?-boswellic acid) can inhibit the enzyme partially the 11-keto group appears to enhance potency. The inhibitory potential of Boswellic Acids on 5-LOX is nonredox in nature. 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); 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. 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; with another author suggesting that their unpublished data is in accordance.
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, which has been noted in vivo in mice given the boswellic acid AKBA in 100umol/kg injections 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) and may also directly bind to Lipopolysaccharide (LPS; a bacterial toxin that induces nF-kB). ?-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. 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). Both studies noted that nF-kB translocation induced by interferons (IFN-?) was unaffected by Boswellic acids.
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.
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. Cathepsin inhibition is a therapeutic target for antiinflammatory actions in neutrophils (immune cells). 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, 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. MPE2S inhibition is an antiinflammatory therapeutic target. 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.
Human Leukocyte Elastase (HLE) is also inhibited by Boswellic acids. 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), 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). 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) and have been replicated elsewhere, and this was thought to be secondary to inhibiting C3-convertase in vitro.
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%, Azathioprine at 200mg/kg as an active control reduced hemagglutinating antibody titres by 10.4%.
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). 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%.
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.
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.
May augment vaccine efficacy, but no oral studies have been conducted
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. 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). 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. 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. This same study noted a proliferation of both CD4 and CD8 positive lymphocytes.
Mixed results in regards to lymphocyte proliferation, but appears to stimulate proliferation (pro-immunity result)
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.
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. 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  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.
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. 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).
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