Bhringaraj

Eclipta Alba (of the family Asteraceae) is a herb called bhringraj in Ayurveda and is most well known for being a liver tonic and beneficial for hair.^[1] It has also been used for anti-viral and anti-venom purposes (usually snake venom), with preliminary evidence for the latter claim^[2] and a fair bit of evidence for the former (see section on the liver). This herb appears to be said to be the best Ayurvedic option for liver cirrhosis and infective hepatitis.^[3]

Other names for this herb include Trailing Eclipta,^[4] Bhringaraja^[5] and Eclipta Prostata appears to be synonymous.^[3]

Eclipta Alba may also kill mosquitoes^[6][7] and act as repellant.^[8]

Mostly a liver tonic, sometimed used against venoms and viruses; has some reported eye and hair benefits

• The coumestans Wedelolactone and Desmethylwedelolactone,^[3][9][1] which can reach 15.9% and 3.5% of ethyl acetate extractions and 1.6% Wedelolactone content in ethanolic fractions.^[3] These tend to be seen as the active ingredients
• Wedelic Acid^[10]
• Echinocystic acid (triterpene saponin) and glycosides thereof
• Verazine ((20S,25S)-22,26-iminocholesta-5,22(N)-dien-3β-ol) and 5 derivatives^[11][12]
• Other triterpenoids such as ursolic acid, α-Amyrin,^[13] or Oleanolic Acid^[13]
• The flavonoid Apigenin^[1] and its 7-O-Glucoside^[10]
• The flavonoid Luteolin^[1] and its 7-O-Glucoside^[10]
• Protocatechuic acid and 4-hydroxybenzoic acid^[3]
• Eclalbasaponin I-II,^[14] III,^[15] IV,^[16] V (possesses a sulfate group),^[15] and both Ecliptasaponin D^[17] and Eclalbatin^[13] (all glycosides of Echinocystic Acid)
• β-Sitosterol,^[9] Daucosterol,^[18] and Stigmasterol^[14]

Main bioactive is thought to be Wedelolactone (and by extension, Desmethylwedelolactone). The alkaloids that are built off of Echinocystic Acid (Ecliptasaponin, Eclalbatin, and Eclalbasaponin I-V) may also be relevant as they are unique to this herb

It should be noted that both Wedelolactone and Desmethylwedelolactone have trypsin inhibitory potential (2.9 and 3.0ug/mL respectively);^[19] this may reduce dietary protein absorption.

One trial attempting to detect a nicotine content of Eclipta Alba (which is reported at times) failed to find such a content.^[10]

A water extract of Eclipta Alba at 100-200mg/kg bodyweight given to rats orally 60 minutes prior to an Elevated Plus Maze test (assessing transfer latency) noted a significant decrease in transfer latency in a dose-dependent manner, with only 200mg/kg being statistically significant (outperforming control by 19% on day one and by 35% on day two).^[20] Dose and time dependent improvements in memory also appeared in mice given a spatial habitual learning test with the same 100-200mg/kg bodyweight dosing.^[20]

Another trial in rats noted that ingestion of 300mg/kg aqueous extract or 30mg/kg Hydrolyzed extract improved performance on Cook's Pole Apparatus, indicative of nootropic potential; Eclipta Alba underperformed relative to the active control Piracetam at 100mg/kg.^[21]

Possible enhancement of learning at high doses, seems pretty weak when compared to even a low dose of Piracetam

One study assessing anxiolytic potential of Eclipta Alba failed to note any reductions in anxiety at 30-300mg/kg of the water or hydroalcoholic extracts, although no reduction in locomotor ability or motor control occured either.^[21] Some anti-stress parameters were noted, with 300mg/kg water extract and 30mg/kg Hydrolyzed extract reducing cold-shock induced ulcer size, but to a lesser degree than 2mg/kg Diazepam.^[21]

No notable effects on anxiety or stress at this moment in time

Eclipta Alba hydroalcoholic extract at 250-500mg/kg given for 10 days prior to bilateral common carotid artery (BCCA) injury and 4 hours of reperfusion noted that Eclipta Alba at both doses was associated with improvement in oxidative biomarkers in the brain (MDA, SOD, Glutathione enzymes) although weaker than the active control of 20mg/kg Quercetin injections.^[22] 500mg/kg Eclipta Alba appeared to reduce edema to the same degree as the active control, and was similar in regards to reducing the measurable size of the infract (although trended to be less potent).^[22]

Appears to be able to protect the brain from neural injury (via antioxidative purposes supposedly), but does not appear to be too potent relative to Quercetin injections

A rat study on maternal aggression using 100-500mg/kg water extract of Eclipta Alba for a period of 15 or 30 days noted that supplementation dose-dependently reduced aggression in mother rats with the highest dose (500mg/kg) being equally effective as 1mg/kg Diazepam as active control.^[4] Specifically, the test was placing an unknown intruder male rat into the cage on postpartum days 4 and 8 (when aggression is usually highest) and observing how frequently the mother attacks this rat; quantifying the bites, flanks, lunges, and how long it takes to attack.^[4] These anti-aggressive effects have been noted previously in male rats at 100-200mg/kg in response to a foot shock test, and at 200mg/kg in a water competition test (competing with other rats for limited access to water).^[23]

Appears to have anti-aggressive actions, which may be related to anxiety reducing actions; bioactive is currently unknown, and there it appears to be as anti-agressive as Diazepam at 1mg/kg in rats

In Ayurveda, the leaves of fresh Eclipta Alba have been rubbed against gums to alleviate toothaches due to their purported analgesic effects.^[24] A subsequent tested was conducted with the ethanolic fractions in mice in a battery of pain tests (tail flick, writhing method, tail pinch method) Eclipta appeared to have dose-dependent pain reducing effects attributable to the alkaloids, with 500mg/kg ethanolic extract or 150mg/kg alkaloids outperforming 50mg/kg Codeine (tail pinch test) and 300mg/kg Aspirin (tail flick test and writhing test); 250mg/kg ethanolic extract of Eclipta Alba was equally effective to the reference drugs.^[24] One comparative study (assessing pain relieving plants of Brazilian medicine) using the leaves of Eclipta Alba (100-200mg/kg hydroalcoholic extract orally) noted that although the pain-reducing effects were replicated in an acetic acid writhing, formalin test that it underperformed to both Morphine (2.5mg/kg) and Justicia pectoralis; Eclipta Alba was the most effective herb in a carrageenan-induced edema test, but underperformed Indomethacin (2mg/kg),^[25] and elsewhere it has been noted that moderate doses of Eclipta (200mg/kg ethanolic extract) are comparable, but not greater, than the active controls of Aspirin and Morphine.^[26]

Naloxone (1mg/kg) did not abolish the effects of Eclipta Alba, suggesting the observed effects are not opioid related.^[25] The combination of Eclipta Alba with Aspirin or Morphine does not appear to enhance the effects of the two pharmaceutical painkillers.^[26]

Appears to have pain killing effects, with 200mg/kg of the ethanolic extract in rats (32mg/kg) being as potent as Aspirin in one study and 500mg/kg of the ethanolic extract (80mg/kg) being more potent. Limited evidence in assessing exactly how potent it is, but the pain reducing effects appear to be repeated and reliable in rats; no human evidence

One intervention in persons with mild hypertension given 3g of the leaves of Eclipta (quite literally crushed powder in capsules, no extraction) daily with 1g at each main meal for a 60 day single blind trial noted that systolic blood pressure was reduced 19% and diastolic 11% relative to placebo (with no effects at the 15 day timepoint).^[27] A time-dependent reduction in mean arterial pressure was noted.^[27]

One study noting reductions in blood pressure, may be related to the diuretic effects (see the section on the bladder)

In mildly hypertensive adults, 3g Eclipta Alba for 60 days is able to reduce triglycerides from 145.19+/-38.66mg/dL to 124.90+/-36.83mg/dL (-14%) while reducing lipid peroxides 18% (an antioxidative effect);^[27] LDL and vLDL were also reduced 25% and 14% with no influence on HDL-C.^[27]

May reduce cholesterol and triglycerides in humans, only one pilot study and no animal evidence

There appear to be α-glucosidase enzyme inhibitors in Eclipta Alba, with one compound called Eclalbasaponin VI being the most potent with an IC₅₀ value of 54.2+/-1.3mM via uncompetitive inhibition.^[16] An ethanolic extract in general inhibits 85% of the enzyme at 100µg/mL (IC₅₀ 54µg/mL) via noncompetitive inhibition.^[28]

At least one study notes an acute reduction of blood glucose by 10.8-17.6% in diabetic rats following 100-250mg/kg of an ethanolic extract of Eclipta Alba when measured 5 hours after ingestion of the extract and a sucrose challenge, which was comparable to Arcabose at 100mg/kg (19.8%).^[28]

Some compounds in Eclipta Alba may inhibit starch digestion and absorption, with at least one study suggesting that this inhibition is comparable to Arcabose when 250mg/kg of the ethanolic extract is compared against 100mg/kg Arcabose

The ethanolic extract of Eclipta Alba appears to inhibit the Aldose Reductase enzyme with an IC₅₀ value of 4.5µg/mL, with 10µg/mL inhibiting 88.6% of the enzyme's activity; this outperformed the active control of Quercetin dehydrate (20µM).^[28]

May also inhibit the Aldose Reductase enzyme, seemingly potent at doing so

One study giving either 100mg or 250mg/kg bodyweight of an ethanolic Eclipta Alba extract to rats over 21 days noted reductions in blood glucose (19%), insulin (10.4%), Urea (30.5%), Uric Acid (33%), and Creatinine (32%) with no significant change in HbA1c, suggesting some glucose lowering effects but more relevant renoprotective effects; the authors thought this was indicative of Aldose Reductase inhibition.^[28]

In alloxan-induced diabetic mice, higher doses of the leaf extract of Eclipta Alba (2-4g/kg) over 60 days was able to reduce fasting blood glucose (60-69%) and HbA1c (50-53%) which was thought to be due to lower activities of the hepatic gluconeogenetic enzymes glucose-6-phosphatase (G6P) and fructose 1,6-bisphosphatase (F6P).^[29] The blood glucose lowering effects outperformed 600mcg/kg Glibenclamide, although the HbA1c lowering effects were comparable.^[29]

Limited evidence in rats, but currently both studies suggest that the blood sugar lowering effects of Eclipta Alba referenced in Ayurveda appear to exist in rats. Mixed results on HbA1c, and the mechanism underlying this (possibly related to reduced carbohydrate absorption) are still not fully elucidated

A methanolic extract of Eclipta Alba (1.6% Wedelolactone) at 100-500mg/kg bodyweight of mice noted dose-dependent immunostimulatory properties, due to an increase in phagocytosis (72-97% increase) with the increase in the antibody titer (157-168%) and white blood cell count (65-67%; 100mg/kg ineffective) increasing with all doses but not in a dose-dependent manner (all doses being of similar potency).^[30] The phagocytosis index increased to a similar degree with the herb Centella Asiatica, but this herb did not influence WBC count of Antibody Titer.^[30]

Appears to have immunostimulatory properties, may proliferate B-cell count as well as increase macrophage activity

500mg/kg of Eclipta Alba appears to reduce up to 55.85% of the inflammation induced by a carrageenin-induced paw swelling test (where edema correlates with inflammation), but failed to outperform the active control of Indomethacin (61.30% inhibition).^[31]

Potential anti-inflammatory properties in response to toxins, but does not appear to be remarkably potent

In response to CCl₄ injections (research hepatotoxin), Eclipta Alba is able to exert hepatoprotective effects that appear to be related to the Wedelolactone, Desmethylwedelolactone, and flavonoid content.^[32] The ethyl acetate fraction (concentrated Wedelolactone) on reducing damage to hepatocytes by CCL₄ or alcohol in vitro appears to be statistically significant at 0.1mg/mL, and at 1mg/mL is more hepatoprotective than Silybin (component of Milk Thistle) and in response to phalloidin (hepatotoxin from death cap mushroom) complete protection is noted at 31ug/mL with 50% cytoprotection at 8ug/mL.^[3] Desmethylwedelolactone is comparatively potent, although Wedelolactone in response to CCL₄ toxicity was the only compound to have significantly protective effects at 0.01mg/mL.^[3]

This protective effect has been noted in a living model, where rats injected with CCL₄ had a 77.7% mortality rate was reduced to 22.2% after ingesting 6.6mL/kg leaf extract (since 180mL was made from 250g leaves, this is about 9.2g/kg) three times prior to insult (48, 24, an 4 hours prior to injections).^[33] ALP, AST, and ALT were reduced by 55%, 42%, and 59% respectively and there appeared to be markedly less damage when histology was observed.^[33] Another study injecting CCL₄ into rats who merely consumed 500mg/kg of the 1:1 water:ethanolic extract daily for 15 days prior to the toxin significantly reduced the CCL₄ induced increase in alkaline phosphatase and amidopyrine N-demethylase, the former to near baseline levels, with some preservation of G6P activity.^[34]

Hepatoprotective effects are possibly synergistic either or both Phyllanthus fraternus and Curcumin,^[35] and are comparatively greater than both Tephrosia purpurea and boerhaavia diffusa.^[36]

Has protective effects against the liver (in vitro) in response to toxins, with preliminary evidence suggesting greater potency that Milk Thistle

Echinocystic acid and its glycosides, mostly Eclalbasaponin II, appear to reduce hepatic stellate cell proliferation in a dose and time dependent manner, with Eclalbasaponin II being as potent as 18β-Glycyrrhetinic acid at 100uM.^[15]

Appears to have some anti-fibrotic effects

The RNA dependent RNA polymerase (RdRp) activity of HCV replicase (NS5B) appears to be inhibited by a water extract of Eclipta Alba with an IC₅₀ value of 11μg/mL; this was confirmed in cell cultures where 130μg/mL inhibited 95% of replication over 48 hours of observation.^[1] This concentration-dependent inhibition of hepatitis replication appeared to be due to Wedelolactone (IC₅₀ 7.7μM) where 10μM inhibited more than 80% of NS5B expression and 50μM abolished expression, while replication was inhibited 30% and 80% respectively; Luteolin and Apigenin also shared this activity, but were significantly weaker (IC₅₀s above 50μM) although combining Wedelolactone with luteolin in a 1:1 ratio reduced the IC₅₀ to 4.5μM and pairing Luteolin with Apigenin resulted in synergism (IC₅₀ 24.6μM).^[1]

Appears to have potential to inhibit hepatitis viral replication, with the main bioactive (Wedelolactone) being synergistic with other components of Eclipta Alba (Luteolin)

3g of the leaves of Eclipta Alba appear to have a diuretic effect, where after 60 days of supplementation mildly hypertensive adults had a 34% greater 24-hour urinary excretion than baseline, and significantly higher than placebo (which was 8.1% higher than their own baseline).^[27] Decreased potassium and increased sodium urinary losses with concomitant increases in serum potassium (3.98mEq/L to 4.92mEq/L; 24% increase) and reduction in serum sodium (159.29mEq/L to 138.71mEq/L; 13% decrease), the authors thought the high potassium content of the leaves may have contributed.^[27]

On average, frequency of urination was not altered; 2/30 subjects reported increased frequency as a side-effect.^[27]

Appears to have diuretic effects, and has been confirmed in humans at 3g of the leaves daily

One human study (single blind) using 3g Eclipta Alba for 60 days reported that 4 our of 30 participants using Eclipta reported improvements in vision as a side effect with nobody in placebo reporting so.^[27]

Limited evidence for the traditional medicine claim that Eclipta improves eyesight, but a side-effect noted in the only human intervention (3g Elipta Alba daily for 60 days) was 4/30 participants (blinded to the treatment) reporting improved eyesight

In HepG2 carcinoma cells, Eclipta Alba ethanolic extract appears to inhibit cell proliferation with an IC₅₀ of 22+/-2.9μg/mL.^[37] A concentration-dependent increase in DNA fragmentation was observed in all tested cells in this study (HepG2, Glioma, and Kidney) although HepG2 was most sensitive, and may be related to NF-kB inhibition which was noted.^[37]

In C6 glioma cells, Eclipta Alba ethanolic extract appears to inhibit cell proliferation with an IC₅₀ of 25+/-3.6μg/mL.^[37]

In isolated rat kidney cells (A498), Eclipta Alba inhibits cell proliferation with an IC₅₀ of 50+/-8.7 μg/mL.^[37]

In pigmented C57/BL6 mice noted that the methanolic extract of Eclipta Alba, when applied topically the extract was able to promote hair follicle transition from telogen to anagen phase and induce hair growth in a dose dependent manner (1.6-3.2mg per 15cm²) and immunohistological staining for the hair growth indicators FGF-7 and Shh were noted.^[38] The percent Anagen induction was similar to the active control of 2% Minoxidil at 87.5%.^[38] Another study in normal Albino male rats has used Eclipta Alba petroleum ether extract (2 or 5% of solution; 1.9+/-0.2% Wedelolactone and 4.56% β-sitosterol) noted that both 2 and 5% of this petroleum ether extract were comparable in potency to 2% Minoxidil when assessing the percentage of hairs over a certain length after 30 days of supplementation, and nonsignificantly outperformed Minoxidil when it came to the percentage of hair follicles in Anagen phase (indicative of growth) after 30 days.^[9]

Eclipta Alba is one of the three herbs (the other two being Citrullus Colocynthis and Cuscuta Reflexa) where the petroleum ether extracts of all three were similarly effective at improving qualitative hair growth when comparing ratios (1:2:3, 2:3:1, or 3:1:2 respectively), but the extract with a 3:1:2 ratio favoring Cuscuta Reflexa at the expensive of Citrullus noted the quickest rate of hair regrowth onset (outperforming 2% Minoxidil) and was quickest in completing hair regrowth after hair removal (again outperforming Minoxidil).^[39] The percent of hair follicles in Anagen phase (indicative of hair regrowth) was increased from 47% in control to 83% (Minoxidil at 67%).^[39]

Hair growth potential of Eclipta Alba extracts (ethanolic, and to a greater extend Petroleum) appear to be comparable to Minoxidil (Rogaine). Combination therapy with a 3:2:1 ratio of Cuscuta Reflexa, Eclipta Alba, and Citrullus Colocynthis (totalling 5% solution, all petroleum ether extracts) appears to be significantly better than Minoxidil according to one study

Piper longum (Long Pepper, not to be confused with Piper Nigrum which is Black Pepper) appears to have synergistic anti-oxidant potential with Eclipta Alba in vitro.^[40]

Up to 2g/kg of a water extract of Eclipta Alba for 14 days in mother rats was not associated with any overt toxicological signs or symptoms (rat pups not assessed).^[4]

One case study cited hepatotoxicity associated with Ayurvedic supplementation, of which Eclipta Alba and bacopa monnieri were possibly contained in a 'Brahmi' supplement being somewhat related; the likelihood of this compound causing hepatoxicity was lesser than Bakuchi tablets containing Psoralea corylifolia.^[41]