Nature: sweet, bitter, cool

Enters: Liver

Actions: Calms the liver and subdues yang; clears heat and promotes urination; nourishes the heart and quiets the spirit. Lowers blood pressure.

Indications:
• Liver yang rising: dizziness, hypertension, etc.
• Drunk by older people in China as a general health tonic to prevent the problems of aging.
Flaws: Luo Bu Ma (Herba Apocyni Veneti) may be unknown to many students and younger practitioners of Chinese medicine. In part, this is because it is not found in most entry-level Chinese materia medica, nor is it found any major traditional Chinese formulas. However, I think it is a good medicinal to know about. It is included in Bensky et al.’s Chinese Herbal Medicine: Materia Medica, 3rd edition (pages 976-977). In that book, Luo Bu Ma is categorized as a wind-extinguishing medicinal (xi feng yao). According to Bensky et al., it is sweet, bitter, and cool and enters the liver. (Other Chinese sources say this medicinal is bland and astringent. Such differences of opinion are common for relatively “new” Chinese medicinals). Luo Bu Ma levels or calms the liver and subdues yang, clears heat and promotes urination, and nourishes the heart and quiets the spirit (although I’m not convinced about these last functions; more to say about that below).

Luo Bu Ma was, up until recently, a folk medicinal mostly found and drunk as a healthy beverage tea in Inner Mongolia. However, recently, this medicinal has been found to lower blood pressure, lower bad cholesterol at the same time as raising high density (good) cholesterol, reduce edema due either to kidney or heart dysfunction, enhance immunity, and promote longevity. Therefore, this herb is now often drunk both preventively and remedially by the middle-aged and elderly in China and Japan. (The first anti-aging research I can find on this medicinal published in China dates from 1990.)

Research on Luo Bu Ma has been conducted in China, Korea, Japan, and several Western countries. This research shows that this medicinal definitely lowers blood pressure (by increasing nitric oxide and thus vasodilation) and has diuretic, cardiotonic, and antioxidant activity. Other research indicates that Luo Bu Ma has antidepressant potential and can reduce anxiety (in mice, equal to benzodiazapines). Yet other research shows that this medicinal is effective for hypercholesteremia and the prevention of atherosclerosis. A water infusion of this herb has been shown to be hepatoproctective in mice. As if that weren’t enough, Luo Bu Ma can reduce the formation of advanced glycation endproducts which are largely involved in the pathogenesis of diabetic vascular complications. Chinese research suggests that the active ingredients in Luo Bu Ma mainly consist of rutin, d-catechin, and quercetin. However, Japanese research shows that Luo Bu Ma contains more than 15 kinds of phenolic constituents.

The root of this plant contains cardioglycosides and is, therefore, potentially toxic. The leaves, however, do not contain the same cardioglycosides or at least contain much fewer of them. Thus the leaves are considered safe to use even long-term. In fact, Zhang Yun-ru says that its leaves are non-toxic (Bensky, p. 977).

As for Luo Bu Ma nourishing the heart and quieting the spirit, because this medicinal is antidepressant and anxiolytic, it is tempting to make that assumption. However, not all Chinese sources on this medicinal include this function, and I believe it is a species of “over-diagnosis.” The fact that Luo Bu Ma clears heat from the liver appears to be unanimous in the Chinese language Chinese medical literature, and heat ascending (mainly from the liver) to harass the heart is one of the three main proximate causes of the heart spirit stirring frenetically. By clearing this heat, the heart spirit is automatically quieted. However, this does not mean that the medicinal should be thought of a heart-nourishing, spirit-quieting medicinal. In Chinese medicine, there are two kinds of spirit-quieting medicinals: 1) those that nourish the heart and quiet the spirit and 2) those that heavily settle and quiet the heart. Heart-nourishing spirit-quieters tend to nourish and enrich heart blood and yin, and I see nothing in any descriptions of this medicinal that suggest it nourishes yin-blood. I think all this medicinal’s empirical effects can be encompassed by the functions of clearing heat, extinguishing wind, and promoting urination.

This medicinal is included in several Chinese ready-made or so-called patent medicines for hypertension. However, you might consider adding it to other standard formulas based on pattern discrimination when the major complaint is high blood pressure and liver heat, liver yang, or liver wind are playing a part in the overall disease mechanisms. It may also be drunk as a tea (infusion) as a daily beverage in the middle-aged and elderly who, by nature, tend to suffer from a surplus in the liver.

Examine.com:

This plant has similar bioactives to Hypericum perforatum [St. John’s Wort] and while drug-drug interaction tests have not yet shown adverse interactions it is highly plausible that they exist.

At this moment in time there is no optimal dose known for humans, although most of the benefits associated with this plant occur in the rat dosing range of around 25-100 mg/kg and with the water extract of the leaves (ie. the tea). This assumes an estimate human dose of:

• 270-1,100 mg for a 150lb person
• 360-1,400 mg for a 200lb person
• 450-1,800 mg for a 250lb person

These doses are well within the range one would use the leaves to make tea from, suggesting that the food product is active and supplementation may not be needed.

1. Sources and Composition

1.1. Sources

Apocynum venetum (of the family Apocynaceae) is a Traditional Chinese Medicine commonly referred to as Chinese dogbane which has traditional usage for its blood pressure reducing properties secondary to diuresis.^[1] Beyond the cardiovascular benefits, it has traditionally been touted to promote longevity^[2] and treat both nephritis and neurasthenia^[3] but more recently is associated with claims of blood pressure reduction and sedation (which opposes the stimulatory effect of green tea from camellia sinensis due to the Caffeine content).^[4] At times medicinal usage of this plant is seen as interchangeable with poacynum pictum and poacynum hendersonii (of the same Apocynaceae family) due to their visual similarity;^[4] they can be distinguished genetically^[5] or by the hyperoside content.^[6]

It should not be confused with the related plant Apocynum cannabinum (Indian Hemp) nor the related plant Apocynum androsaemifolium, both of which have traditional usage for heart health due to their Cymarin content which is therapeutic at low doses but toxic at higher doses; apocynum venetum does have a cymarin content as well (113?g/g in the leaves)^[7] which is regarded as safe^[4] although the higher levels in the aged stem (1,310?g/g) may not be.

The leaves are sometimes called ‘Luobuma’ (China) or ‘Rafuma’ (Japan), and Luobuma tea refers to the water extract of the leaves.^[8][1] The plant itself is a small herbaceous shrub 1-2 meters tall with purplish red to pink flowers, and bears fruits in autumn 7-8 months after flowering.^[4] The apocynum venetum shrub is surprisingly resistant to drought and stress (sand, winds, and salt), which may underlies its name of “Herbal for Relief of Famines” (Jiu-Huang-Ben-Cao from the Ming Dynasty).^[4]

Apocynum venetum is a small shrub which bears leaves (Luobuma) that are commonly drunk as a tea in order to reduce blood pressure and are claimed to have an added relaxing effect (somewhat opposite of a similar tasting tea, green tea from camellia sinensis); the usage of Luobuma parallels that of Roselle

1.2. Composition

Luobuma (leaves unless otherwise specified) contains:

• Apocynin A-D (very confusing as this is not the apocynin phenolic (acetovallinone) found in other plants)^[9][4]
• Cymarin at 113?g/g in the leaves, lower levels than Apocynum cannabidum^[7] although there are higher levels in the stem (367?g/g) and aged stem (1,310?g/g) as well as the root (195?g/g)^[7]
• Apocyanisode I and II (Ionone glucosides)^[10]
• (+/-)Gallocatechin and (+/-)Catechin^[11]
• (-/-)Epigallocatechin and (-)-Epicatechin^[11]
• (-/-)Epicatechin-()Gallocatechin and Epigallocatechin-()Epicatechin^[11]
• Quercetin^[12][13] and related structures such as hyperoside (Quercetin 3-Galactoside) and isoquercitrin (Quercetin 3-Glucoside);^[3] said to be in comparable levels to that of Hypericum perforatum;^[14] also contains Baimaside (Quercetin 3-O-Sophoroside),^[13] Avicularoside (Quercetin-3-Arabinoside)^[15] Rutin (Quercetin 3-Rutinoside),^[15] and Quercitronic Acid/Querciturone (Quercetin-3-Rhamnoside)^[15]
• Kaempferol^[16] and its 3-O-?-D-glucoside (Astragalin),^[15][13] Trifolin (Kaempferol 3-Galactoside),^[15]
• Apigenin biflavonoids including Amentoflavone and Biapigenin^[15]
• Hyperforin and Adhyperforin;^[15] once novel constituents of Hypericum perforatum
• Procyanidin B2^[11]
• Cinchonain Ia^[17]
• Caffeic acid and 3-O-caffeoylquinic acid^[18]
• Vanillic acid^[13] and Chlorogenic Acid^[16]
• Daucosterol^[13] and both Lupeol and Phytol in roasted leaves^[10]

The overall content of flavonoids is known to heavily rely on growing conditions.^[12]

There is a total amino acid content ranging from 81.76-83.25mg/g (leaf equivalent) but a free amino acid content of 3.85-4.04mg/g, with the most abundant amino acid being glutamic acid (9.82-10.01mg/g total amino acid and 0.29-0.31mg/g free) which was said to confer the Umami taste of the tea.^[19]

The leaves of this plant appear to be high in flavonoids, mostly some catechins (some novel and some in green tea) and a large amount of quercetin variants. There also seems to be a lot of parallels in these constituents and those seen in St.John’s Wort surprisingly, since the plants are not phylogenetically related

2. Molecular Targets

2.1. Ion Channels

Apocynum venetum, in cultured N2A neuroblastoma cells at a concentration of 20µg/mL, has been demonstrated to inhibit steady state sodium channels independent of nitric oxide and with an IC₅₀ of 18.4?g/mL; it was readily reversed with washout and voltage gated sodium channels were unaffected.^[20]

There was a mild inhibitory effect on voltage gated potassium channels (16.2+/-3.7% and 48.0+/-2.9% inhibition at 10 and 30?g/mL) yet none on ATP-sensitive channels.^[20] These effects were lost in the presence of diazoxide, a potassium channel opener.^[20]

The leaf extract of apocynum venetum appears to cause mild inhibitory effects on both potassium and sodium channels at a concentration where blood pressure reduction in noted; this is not dependent on nitric oxide formation

3. Pharmacology

3.1. Phase I Enzyme Interactions

Apocynum venetum has similar bioactives to Hypericum perforatum, raising concerns of possible drug interactions.

When fed to rats at 3.3mg/kg, Apocynum venetum leaf extract failed to alter the pharmacokinetics of nifedipine while 33mg/kg and 15mg/kg St. John’s Wort both trended to reduce plasma concentrations over the next 30 minutes.^[21] Two weeks treatment of 15mg/kg managed to reduce the AUC of nifedipine while 3.3mg/kg apocynum venetum was ineffective.^[21]

May not influence CYP3A activity, although the above study did not test higher (and more practical) doses over two weeks despite trends towards inhibition being present

3.2. Drug Interactions

Apocynum venetum at 3.3mg/kg over two weeks to rats has failed to alter the intestinal permeation of methylprednisone, suggesting no significant influence on the P-glycoprotein transporter.^[21]

No significant influence known with P-glycoprotein transporters

4. Neurology

4.1. GABAergic Neurotransmission

The anxiolytic properties of the leaf extract (100-125mg/kg in mice) doses is fully mediated by the GABA_A receptor, while lower doses (22.5-30mg/kg) are not; this is thought to be due to Kaempferol which is active at 0.02-1mg/kg oral intake.^[16]

Higher doses of this herb appear to have anxiety reducing properties secondary to the kaempferol content acting on the benzodiazepine receptors

4.2. Adrenergic Neurotransmission

A water extract of the leaves for 2-8 weeks in rats noted decreases in noradrenaline at 15-60mg/kg (but not 250mg/kg) in the hypothalamus (8 weeks) and striatum (starting at 2 weeks) by 33-44% in the hypothalamus and 22-39% in the striatum; there was no time nor dose dependence noted.^[3] The decline in noradrenaline and its metabolite (homovanillic acid) during depression, however, are fully preserved with 10 days supplementation of 50-100mg/kg (but not 25mg/kg) in mice.^[22]

While there may be a small suppressive effect on noradrenaline concentrations at rest, the decline seen during depression is greatly attenuated; this suggests a modulatory effect

Adrenergic receptor density does not appear affected.^[3]

No known interactions with adrenergic signalling beyond modifying noradrenaline levels

4.3. Dopaminergic Neurotransmission

L-Tyrosine concentrations in all brain organs does not appear affected with oral ingestion of 15-250mg/kg of the leaf extracts for 8 weeks in otherwise normal rats.^[3]

A water extract of the leaves at 15mg/kg daily for eight weeks was able to slightly reduce dopamine concentrations in the hypothalamus (20%); there was no influence of higher doses (60-250mg/kg) nor lower time frames (2 weeks) and these effects were exclusive to the hypothalamus.^[3] Elsewhere, 50-100mg/kg (but not 25mg/kg) in mice for 10 days preserved the decrease in dopamine concentrations seen in depression.^[22]

DOPAC was slightly reduced when dopamine or noradrenaline were increased^[3] but is significantly preserved in states of depression (when dopamine is also preserved.^[22] Furthermore, the antidepressant effects of 50-100mg/kg of the extract over 10 days in mice appears to be blocked by both D1 receptor antagonists and D2 receptor antagonists.^[22]

Similar to the effects seen with adrenergic signalling, there appears to be little to no effects on dopamine at rest or a small decline in dopamine levels are seen. In states of depression where dopamine would normally be reduced, however, there is a significant preservation of dopamine levels

4.4. Serotonergic Neurotransmission

15-250mg/kg of the leaf water extract for up to 8 weeks in rats does not influence concentrations of serotonin, L-tryptophan, or 5-HIAA.^[3] In depressed mice, 25-100mg/kg of the extract has failed to preserve the reduction in serotonin seen in depression.^[22]

Unlike the influence on catecholamines (dopamine and noradrenaline), the reduction in serotonin seen with depression is not prevented

The lower anxiolytic dose of the leaf extract (22.5-30mg/kg in mice) appears to be mediated by the 5-HT_1A receptors, while higher (100-125mg/kg) doses are not.^[16]

There may still be some serotonergic signalling when it comes to very low doses of this plant and possible reductions in anxiety, although more practical higher doses do not appear to be assocaited with serotonin signalling at all

4.5. Alertness

In a rat antidepressant test there did not appear to be any alterations in locomotion nor defecation (thus, no amphetamine like activity is thought to exist).^[14] In anxiolytic tests (testing for sedation from benzodiazepine like effects) the leaf extract was not significantly different from 1.5mg/kg diazepam at the active doses (22.5-30mg/kg) in altering motor function^[23] nor was the active GABAergic agent Kaempferol (0.02-0.08mg/kg).^[16]

Does not appear to have any significant sedating properties (assessed by locomotor tests) nor amphetamine-like properties when tested in rodents

4.6. Neuroprotection

Mechanistically, hyperoside at 2.5-10?g/mL appears to attenuate the increase in intracellular calcium (PC12 cells) induced by corticosterone (10?M) with a protective effect comparable to 10?M fluoxetine^[24] and thought to be secondary to this there was a preservation of BDNF and CREB activity (greater than fluoxetine but not normalized to control)^[24] associated with a relative preservation of BDNF and MAP4 mRNA levels.^[25]

In the presence of hyperoside, the neurodegenerative effects of corticosterone are attenuated and the antidepressive factors (BDNF, CREB, MAP4) are preserved somewhat

Elsewhere, in vitro with PC12 cells treated with 1-10?g/mL of the herbal extract apocynum venetum appeared to reduce lipid peroxidation to a greater extent than both Ginkgo biloba and St.John’s wort, although 100?g/mL of the extracts were comparable.^[26]

In an in vitro test of oxygen and glucose deprivation (test of benefits against ischemia-reperfusion), 5-50?g/mL of apocynum venetum showed mild protective effects not exceeding 50% cell viability (control at 100% and oxygen deprivation near 30%);^[27] higher concentrations (5-500mg/mL) were not significantly better.^[27]

500mg/kg of the extract in rats prior to ischemia has been noted to improve the neurological score when measured 24-72 hours after ischemia (250mg/kg only active after 72 hours and 125mg/kg ineffective) and was able to half infarct size relative to control.^[28] Alongside the reduced infarct size was reduced edema and brain leakage, which appeared to be associated with preservation of the blood brain barrier’s structure (and reductions of both MMP2/9 and lipid peroxidation).^[28]

Shows some promise against lipid peroxidation and oxidative stressors, and while the potency against oxygen deprivation seems to be less it is relevant in rat models of ischemia where there are minor anti-stroke properties

4.7. Depression

30-125mg/kg of the leaf water extract of apocynum venetum appeared to possess antidepressant effects in the forced swim test with a potency comparable to 20mg/kg Imipramine.^[14] Higher doses of the extract (250-500mg/kg) were ineffective initially but performed equally after two weeks^[14] and 50-100mg/kg of the extract, but not 25mg/kg, has elsewhere been effective in the tail suspension test (more than 5mg/kg fluoxetine) while all doses were comparable to fluoxetine in a forced swim test^[22] and prevented with dopamine receptor antagonists (D1 and D2).^[22]

There appears to be a somewhat respectable antidepressive effect associated with catecholamine metabolism, probably secondary to preventing their decline during stress

4.8. Anxiety

In an elevated maze plus test, mice given 22.5–30mg/kg and 100–125mg/kg of the leaf extract (standardized to 3.5% hyperoside and 3.2% isoquercitrin) experience a reduction in anxiety with the lower dose being more potent (to a comparable level as 1.5mg/kg diazepam and 10mg/kg buspirone).^[23][16] The lower dose hindered by 5-HT_1A receptor antagonists while the higher dose was fully blocked by benzodiazepine receptor antagonists.^[16]

There are anti-anxiety effects associated with the tea, but unlike the antidepressive properties (associated with catecholamines) these seem to be related to GABA and serotonin signalling; it occurs at lower doses than antidepressive effects

5. Cardiovascular Health

5.1. Cardiac Tissue

In isolated atria cells (guinea pig), apocynum venetum causes a cardiotonic effect at 1mg/mL (little to no response at 100µg/mL) yet this was not correlated with the cymarin content of the plant (cymarin being a known cardiac glycoside in this plant species) nor was it blocked by propanolol;^[7] it appears that components of apocynum venetum have PDE3 inhibiting properties, with 1mg/mL of the leaf, root, and stem extracts inhibiting 84-88% of PDE3 activity.^[7]

Preliminary evidence suggests a cardiotonic effect, but practical relevance is unknown (and a high concentration used in the heart, which may not apply to oral supplementation)

5.2. Blood Pressure

While the water extract of the leaves (0.1–10µg/mL) does not influence endothelial function in vitro at rest nor is it active in denuded cells, it appears to concentration dependently inhibit phenylephedrine and U46619 (Thromboxane A2 receptor agonist) in a manner fully dependent on NOS enyzmes.^[1] There is no relaxing effect against endothelium precontracted with potassium, but the effect persisted after two washes of the cells.^[1] The mechanisms are known to involve potassium channels^[29][1] although it is not clear how, although some authors^[1] have noted the atypical mechanisms are similar to both Eucommia ulmoides^[30] and Eleutherococcus senticosus^[31] and apocynum venetum has elsewhere been noted to have mild inhibitory effects on voltage gated but not ATP sensitive potassium channels (not mediated by nitric oxide).^[20]

0.3-10?g/mL apocynum venetum appears to suppress the aortic contractions induced by ACE (Angiotension II),^[32] the peptide of which its inhibition is the current blood pressure reducing therapy. This is thought to be due to inhibiting ACE induced superoxide production (ACE, via acting on the AT₁ receptor, increases NADPH oxidase and O_– production^[33][34] which suppresses nitric oxide^[35]) and induction of nitric oxide synthesis.^[32] Furthermore, the reaction of superoxide and nitric oxide is known to produce peroxynitrite (ONOO^–) which can negatively regulate NOS enzymes^[36] and apocynum venetum directly sequesters these peroxynitrite radicals via its catechins;^[37] sequestering ONOO^– is known to block its suppressive effects.^[36]

Apocynum venetum appears to have blood pressure reducing mechanisms that are within a feasible concentration range, and while the mechanisms are not fully elucidated they appear to be related to nitric oxide signalling, antioxidant effects, and calcium channels

In hypertensive rat models (spontaneously, renal, and salt fed) given 70mg of the water leaf extract of apocynum venetum daily (333-350mg/kg) for 40-100 days, the tea was able to reduce blood pressure in all three rat models more than control and while equally potent to 30mg/kg Captopril in one model (renal hypertensive) it underperformed in the other two.^[8]

In the sodium fed rats, urine output was increased with apocynum venetum (2.1 and 2.6 fold on days 20-60) which did not occur with the roasted leaves;^[8] there were no differences in the magnitude of blood pressure reduction between groups, and increased urination occurred in both groups of the renal hypertensive rats.

Blood pressure reduction has been noted with ingestion of the water extract of the leaves, and this appears to occur to a lower degree than the reference drug but up to two-fold higher doses than the antidepressant effects

5.3. Atherosclerosis

In vitro, LDL oxidation from copper is reduced by 10-100µg/mL of apocynum venetum extract with the higher dose preventing any significant differences from nonoxidized control^[38] and an IC₅₀ value of 68.1µg/mL being determined for the leaf extract (mostly due to chlorogenic acid and epigallocatechin, with IC₅₀ values of 1.9µM and 2.3µM respectively).^[17]

This potent inhibition of LDL oxidation was met with only 39% inhibition of lipid peroxidation (TBARS) and halved the increase in macrophage cholesterol accumulation when LDL and macrophages were in the same culture with copper^[38] (to assess foam cell formation, involved in the pathology of atherosclerosis). Elsewhere, TBARS from LDL oxidation was reduced in a concentration dependent manner between 2.5-200µg/mL (9.8-88.3%) with most inhibitory effects coming from hyperoside, chlorogenic acid, and epigallocatechin.^[17]

May reduce LDL oxidation due to its antioxidant properties, but practical relevance of this information is not known. Possible anti-atherosclerotic properties and reducing plaque formation on arties

6. Interactions with Glucose Metabolism

6.1. Glycation

When investigating the formation of advanced glycemic end products (AGEs) the water extract appeared to inhibit AGE formation with an IC₅₀ value of 37.2+/-0.6µg/mL, which outperformed the reference drug of Aminoguanidine (59.2+/-1.5µg/mL).^[11] This may be related to the known catechins, which had IC₅₀ values between 19.8+/-0.8µg/mL (Gallocatechin) and 9.1+/-0.2µg/mL (Epigallocatechin).^[11]

Possible antiglycative properties, which would reduce AGE formation and may be of use for diabetes or insulin resistance (reducing organ damage, rather than treating the state)

7. Interactions with Oxidation

7.1. Lipid Peroxidation

The aqueous leaf extract at 10mg/kg given to rats after liver damage (from CCl₄) failed to significantly reduce serum MDA levels relative to control, although it trended towards such^[39] and appeared to have antioxidative properties against H₂O₂ and iron in vitro in the range of 15-1,000µg/mL.^[39]

8. Interactions with Organ Systems

8.1. Kidneys

Chronic (20-60 days) ingestion of a nonroasted water extract of apocynum venetum leaves in rats at 335-350mg/kg appears to increase urine output of rats on a high sodium diet (2.1-fold and 2.6-fold on days 20 and 60); this effect was not noted with twice roasted leave.^[8] Oddly, diuresis was increased by both the roasted and unroasted leaves in rats with hypertension secondary to renal damage.^[8]

Appears to be a diuretic at the doses which reduce blood pressure

9. Safety and Toxicology

9.1. General

The LD₅₀ of apocynus venetum appears to be greater than 10g/kg in rats and preliminary genotoxic and teratogenic studies have failed to find any harm associated with the plant,^[4] and later a 30 day test failed to find any abnormalities up to 30g/kg in mice^[40] and in continuing the in vitro studies a lack of genotoxicity was repeated and no abnormalities in sperm cells were noted.^[40]

Preliminary evidence in rodents does not suggest any toxic effects from this plant even at abnormally high oral doses

 

Dose: 3-9g