1.
Sources and Composition
1.1
Sources
Picrorhiza kurroa (of the family scrophulariaceae), also known as Kutki or Katuki, is a perennial herb used in Ayurveda and sometimes used as a substitute for the herb gentiana kurroo; and tends to grow in the Himilaya region on rocky places within 3000-5000m above sea level.[1] It is traditionally used for liver disorders, but has also been implicated in the treatment of upper respiratory tract, fevers, dyspepsia, chronic diarrhea, and scorpion stings[1] as a part of the formulations Arogyavardhini, Tiktadya ghrita, Jatyadi ghrita, Punarnavasava and Nimbadi churna.[2] It is sometimes used interchangeably with the similar herb Picrorhiza scrophulariiflora, which contains the same bioactives.[3]
The plant is also known to be highly bitter (white root moreso than black root) which led to its name (as picros is greek for 'bitter') and appears to be endangered due to overharvesting.[1] It should not be confused with picrotoxin, which is a completely different molecule that also happens to be better (hence the picros).
Picrorhiza kurroa is a bitter herb used in Indian medicine for the purpose of helping the liver and digestion, among other usages. It grows in a limited region and altitude, and is currrently overharvested to an endangered status
1.2
Composition
- The bitter principle known as 'Kutkin',[4] which is a mixture of picroside I and picroside II (kutkoside).[2] These are irioid glycoside structures[5] present at 1.611% and 0.613% of the roots dry weight, respectively[3]
- The α-methoxy substituted catechol Apocynin,[6] structurally similar to vanillic and ferulic acids
- Androsin[7]
- Cucurbitacin glycosides based on cucurbitacin B and dihydrocucurbitacin B[8]
The main ingredients are the two molecules that make up the mixture called kutkin (or picroliv), which are picroside I and picroside II; both molecules are based off the same backbone, but one contains a cinnamic acid group and the other an apocynin group.
1.3
Properties
Storage of picrorhiza kurroa at 50°C for three to six months appears to not result in any significant degradation, although storage at 60°C for this time frame resulted in a 30-50% rate of degradation.[9]
Higher than average temperatures may degrade the bioactives in the plant. While refrigeration does not appear to be necessary, it may be prudent to store it away from heat producing appliances
1.4
Variants of Supplementation
Picroliv is a mixture of kutkin (picroside I and picroside II) in a 1:1.5 ratio[10] which has a slightly higher concentration of picroside II than does basic kutkin (45:55).[2] 60% of the mixture by weight is picrosides I and II, with the other 40% being micellaneous irioid glycosides.[11]
Picroliv is another name for kutkin, and while kutkin tends to have a more balanced profile picroliv tends to favor a higher concentration of picroside II
Picrolax is a brand name for an extract of Picrorhiza kurroa which is recommended for laxative purposes. This extract appears to confer 45mg picroside I (0.02%) and 17.6mg picroside II (0.01%) for every 1.585g of supplement[2] suggesting that other bioactives play a more significant role.
Picrolax is a form of picrorhiza kurroa that is sold for its laxative purposes; it has a low concentration of kutkin but high enough doses may still be hepatoprotective
2.
Pharmacology
2.1
Absorption
Irioid glycosides (picroside I and picroside II) are known to be able to be hydrolyzed in the intestines leading to their aglycones, as evidenced by aucubin.[12] This is hypothesized to partly underlie the poor oral bioavailability of picrosides[2] which is common among most irioid glycosides.[13][14][15] Isolated kutkin has a poorer bioavailability than does the plant extract however,[2] suggesting some synergism between components of the plant.
Like most irioid glycosides, the picrosides (components that make up kutkin) appear to be poorly absorbed. The exact bioavailability was not calculated
2.2
Serum
Following ingestion of Picrorhiza kurroa, picroside I has been detected in the blood at a Cmax of 206.10+/-7.09ng/mL (45mg/kg via 100mg/kg kutkin), a Cmax of 357.88+/-5.74ng/mL (same dose via 510mg/kg plant extract), and a Cmax of 301.43+/-9.19ng/mL (same dose via 1.585g/kg picrolax).[2] All Tmax values were approximately one hour, and the half-life was 50-56m for mixtures and 37m for pure kutkin.[2]
Following ingestion of Picrorhiza kurroa, picroside II has been detected in the blood at a Cmax of 152.62+/-11.54ng/mL (55mg/kg picroside II via 100mg/kg kutkin), a Cmax of 134.67+/-18.18ng/mL (32.3mg/kg via 510mg/kg plant extract), and a Cmax of 76.64+/-3.69ng/mL (17.6mg/kg via 1.585g/kg picrolax).[2] Picroside II also has a Tmax of approximately one hour, but a shorter half-life between 15-30m.[2]
Picrosides reach serum at a low nanomolar concentration
2.3
Metabolism
Picroside II appears to be predominately (80%) conjugated in the blood as either a glucoronide or sulfate, with 20% of circulating picroside II being eliminated in its free form.[16]
Picrosides appear to be conjugated by Phase II metabolic enzymes
3.
Cardiovascular Health
3.1
Triglycerides and Lipoproteins
In mice given a high fat diet, 50-200mg/kg of picrorhiza kuroa daily for 12 weeks appears to be able to normalize most parameters of lipid metabolism (triglycerides, cholesterol, LDL-C) although without apparent influence on HDL-C; these changes were thought to be secondary to aiding the liver[17] and has been seen elsewhere with lipid alterations induced by PX-407.[18]
Secondary to helping the liver, there may be reductions in circulating triglycerides and LDL cholesterol
4.
Interactions with Glucose Metabolism
4.1
Diabetes
100-200mg/kg of a water extract of picrorhiza kurroa over the course of 14 days in diabetic rats (streptozotocin induced) is able to improve blood glucose and insulin levels in a dose-dependent manner, with the 200mg/kg dosage being nonsignificantly less potent than the reference drug of 10mg/kg glibenclamide.[19]
There may be antidiabetic properties of the plant, but they are mostly unexplored and trend to underperform relative to the reference drug glibenclamide
5.
Inflammation and Immunology
5.1
Mechanisms
Apocynin appears to be able to inhibit NADPH oxidase in neutrophils in vitro at 4µg/mL concentration, with a potency somewhat comparable to 20µg/mL vanillic and ferulic acids[20] and appears to be effective in microglia at 500µM.[21]
Oral ingestion of apocynin at 100mg/kg thrice daily alongside MPTP toxin (to induce parkinson's like effects via microglia activation) was able to alleviate symptoms, which was attributed to NADPH oxidase inhibition.[6] NADPH oxidase activation is known to be involved in the pathology of MPTP[21] and protective effects have been noted with other NADPH oxidase inhibitors such as Spirulina.[22]
Apocynin appears to be an NADPH oxidase inhibitor, albeit significantly weaker than the reference supplement (C-phycocyanobilin from spirulina)
5.2
Immunosuppression
200mg/kg of the rhizome of kutki for 14 days prior to immunosuppression (cyclophosphamide) is able to partly preserve the reduction in antibody titer seen in immunosuppressed control and slightly increased antibodies in control mice.[23]
There appears to be an increase in antibodies in mice given oral supplementation of the plant, and this may occur with and without immunosuppression
5.3
Asthma
A phenolic glycoside known as androsin found in picrohiza kurroa appears to be able to reduce allergic reactions at an oral dose of 10mg/kg in guinea pigs an hour prior to inhalation challenge[7] or 500µg inhalative.[24]
One study using a combination supplement of picrorhiza kurroa (270mg of 30% apocynin), ginger (100mg of 5% gingerols), and ginkgo biloba (130mg of 24% ginkgoflavones) taken twice daily for 20 weeks failed to note any significant benefit on Peak Expiratory Flow Rate (PEF) or FEV1 and only trends to improve asthmatic symptoms.[25]
No significant known interactions with asthma
5.4
Virology
An ayurvedic mixture of herbs (Arogya-wardhani) of which is 50% picrorhiza kurroa by weight has been noted to have efficacy against acute viral hepatitis[26] and when 375mg of picrorhiza kurroa thrice daily for two weeks (daily dose of 8.16-8.64mg picroside I and 16.5-18mg picroside II) was able to reduce serum bilirubin and enzymes in a time dependent manner.[9]
The lone human study noted that the well known hepatoprotective effects applied to humans with acute viral hepatitis over the course of two weeks of supplementation
6.
Interactions with Organ Systems
6.1
Liver
Picroliv (25mg/kg) orally to rats for six weeks effectively abolished (over 90% normalization) the changes induced by aflatoxin despite not having a significant effect on rats not given aflatoxin[27] and this potency against aflatoxin specifically has been replicated elsewhere with comparable potency to 20mg/kg silymarin (from milk thistle, comparable molar doses) although the 84-100% protection seen with picroliv was less variable than silymarin (53-100%) and while silymarin was more effective at reducing lipid peroxidation picroliv is more effective at reducing liver enzymes (GPT and ALP).[28][11] Picroliv appears to be effective when given prior to the toxin[27] and when given after toxin exposure for one week,[29] two weeks,[11] and six weeks.[28]
Although most studies assess the protective effects of picroliv against aflatoxin it has also shown protective effects against oxytetracycline (at 1.2-12mg/kg picrolive),[30] carbon tetrachloride (12mg/kg picroliv),[31][32] thioacetamide,[33] paracetamol,[34][35] cadmium,[36][37] ischemia[38] and partial hepatectomy,[39] monocrotaline,[40] hydrazine,[41] galactosamine (12mg/kg picroliv),[42][9] and alcohol.[43] Most notably, picroliv also appears to be protective against poisoning from the deathcap mushroom (Amanita phalloides) with protective effects comparable to silybinin yet greater rehabilitative effects.[44]
When looking at the studies on alcohol specifically when thirty days of alcohol ingestion (3.76g/kg in rats) was followed up with coingestion of alcohol and 12mg/kg picroliv for 15 days, picroliv was able to attenuate the adverse changes (although not absolute protection)[43] although 45 days of continuous ingestion at 12mg/kg caused full protection (3mg/kg causing 36% protection).[45]
Picroliv (picrosides I and II) appears to be very potently protective of the liver in rats, in accordance with its claims in ayurvedic medicine. The protective effects seem to extend to pretty much every liver stressor tested, and seems to persist when taken either in a prophylactic (preventative) or rehabilitative manner
In general, when picroliv is used at the higher dosage (25mg/kg oral ingestion) and compared to an equimolar dosage of silymarin (20mg/kg) they are comparable in protective effects[28][11] but when lower doses of picroliv (12.5mg/kg or less) are compared against an equimolar dose of silymarin (10mg/kg or less) picroliv appears to be more potent.[30] Doses in the 50-100mg/kg range for picroliv are still comparable to equimolar doses of silymarin, and is also comparable to curcumin and ellagic acid.[32][34]
When compared to other hepatoprotective agents, picroliv appears to be as potent as silymarins (from milk thistle) when they are compared at higher doses and stronger when they are compared at lower doses
Picroliv possesses chloretic and anticholestatic potential in rats treated with paracetamol and ethynyl estradiol,[35] CCl4,[46] alcohol,[45] and cadium.[36][37] In this regard, supplementation of 3-6mg/kg to rats is effective yet there markers of cholestasis are fully normalized with prolonged ingestion (2 weeks or longer) of 12mg/kg picroliv[46][45] and seems more potent than an equimolar dose of silymarins.[35]
There appears to be an anticholestatic potential for picroliv in instances of liver damage which is maximized (absolute protection) at a chronic rat intake of 12mg/kg. This potency exceeds silymarins from milk thistle
When looking at fatty liver (steatohepatitis) in rats fed a high fat diet, 200-400mg/kg of a 50:50 ethyl alcohol:water picrorhiza kurroa extract (6.54% picrosides) is able to significantly reduce liver fat over the course of four weeks supplementation, with the higher dose having a greater potency than 50mg/kg silymarins.[47] The increase in liver fat from changing to a high fat diet in rats was fully prevented, and the picrorhiza kurroa group ended up with 42% the liver fat seen in the control group.[47]
Steatohepatitis induced by hydrazine is also prevented with supplementation of picrosides at 50mg/kg.[41]
The liver protective effects seem to extend to reducing fatty liver, where picrorhiza kurroa seems very effective at preventing fatty liver (its benefits also seem general rather than specific for a particular cause of fatty liver)
6.2
Intestines
In inflammatory bowel diseases (ulcerative colitis), the release of inflammatory cytokines such as IL-1β and TNF-α are involved in pathology[48][49] and suppressing their release via inhibiting NF-kB is seen as therapeutic.[50][51]
In a mouse model of dextran-sulfate-sodium (DSS) induced colitis, supplementation of 12.5mg/kg picroliv for seven days following DSS ingestion (for seven days prior to picroliv and continued throughout supplementation) was able to attenuate the reduction in colon length and improve histological scores by about half.[10] These benefits correlated with less NF-kB mRNA induction and less release of inflammatory cytokines (IL-1β and TNF-α) and oxidation.[10]
Appears to have moderately potent antiinflammatory effects in an animal model of ulcerative colitis
6.3
Kidney
The alterations seen in kidney oxidative markers from aflatoxin are potently suppressed with ingestion of 25mg/kg picroliv in rats for 14 days after aflatoxin ingestion, with a potency somewhat comparable to 20mg/kg silymarin.[11] When comparing the protective effects in the liver against the protective effects in the kidneys, picroliv seems slightly more effective in protecting the liver (in a model of cadmium toxicity).[37]
The liver protective effects may also extend to the kidneys, suggesting a general protective effect against organ function
7.
Interactions with Aesthetics
7.1
Skin
Supplementation of 200mg of the dried rhizome twice daily alongside methoxsalen therapy was able to significantly reduce symptoms of vitiligo, with 10% of the group nonresponsive to picrorhiza kurroa intervention and 27% of the group experiencing complete resolution of symptoms.[54]
References
- ^[No authors listedPicrorhiza kurroa. MonographAltern Med Rev.(2001 Jun)
- ^Upadhyay D, Dash RP, Anandjiwala S, Nivsarkar MComparative pharmacokinetic profiles of picrosides I and II from kutkin, Picrorhiza kurroa extract and its formulation in ratsFitoterapia.(2013 Mar)
- ^Tiwari SS, Pandey MM, Srivastava S, Rawat AKTLC densitometric quantification of picrosides (picroside-I and picroside-II) in Picrorhiza kurroa and its substitute Picrorhiza scrophulariiflora and their antioxidant studiesBiomed Chromatogr.(2012 Jan)
- ^Basu K, Dasgupta B, Ghosal SStructure of kutkin, the bitter glucoside of Picrorhiza kurroa Royle ex BenthJ Org Chem.(1970 Sep)
- ^Kumar V, Sood H, Sharma M, Chauhan RSA Proposed Biosynthetic Pathway of Picrosides Linked through the Detection of Biochemical Intermediates in the Endangered Medicinal Herb Picrorhiza kurroaPhytochem Anal.(2013 May 21)
- ^Philippens IH, Wubben JA, Finsen B, 't Hart BAOral treatment with the NADPH oxidase antagonist apocynin mitigates clinical and pathological features of parkinsonism in the MPTP marmoset modelJ Neuroimmune Pharmacol.(2013 Jun)
- ^Dorsch W, Stuppner H, Wagner H, Gropp M, Demoulin S, Ring JAntiasthmatic effects of Picrorhiza kurroa: androsin prevents allergen- and PAF-induced bronchial obstruction in guinea pigsInt Arch Allergy Appl Immunol.(1991)
- ^Stuppner H, Wagner HNew cucurbitacin glycosides from Picrorhiza kurrooaPlanta Med.(1989 Dec)
- ^Vaidya AB, Antarkar DS, Doshi JC, Bhatt AD, Ramesh V, Vora PV, Perissond D, Baxi AJ, Kale PMPicrorhiza kurroa (Kutaki) Royle ex Benth as a hepatoprotective agent--experimental & clinical studiesJ Postgrad Med.(1996 Oct-Dec)
- ^Zhang DK, Yu JJ, Li YM, Wei LN, Yu Y, Feng YH, Wang XA Picrorhiza kurroa derivative, picroliv, attenuates the development of dextran-sulfate-sodium-induced colitis in miceMediators Inflamm.(2012)
- ^Rastogi R, Srivastava AK, Rastogi AKLong term effect of aflatoxin B(1) on lipid peroxidation in rat liver and kidney: effect of picroliv and silymarinPhytother Res.(2001 Jun)
- ^Transformation of aucubin to new pyridine monoterpene alkaloids, aucubinines A and B, by human intestinal bacteria
- ^Wang CH, Wang ZT, Bligh SW, White KN, White CJPharmacokinetics and tissue distribution of gentiopicroside following oral and intravenous administration in miceEur J Drug Metab Pharmacokinet.(2004 Jul-Sep)
- ^Park EJ, Lee HS, Oh SR, Lee HK, Lee HSPharmacokinetics of verproside after intravenous and oral administration in ratsArch Pharm Res.(2009 Apr)
- ^Li HL, He JC, Bai M, Song QY, Feng EF, Rao GX, Xu GLDetermination of the plasma pharmacokinetic and tissue distributions of swertiamarin in rats by liquid chromatography with tandem mass spectrometryArzneimittelforschung.(2012 Mar)
- ^Li T, Zheng Y, Fu F, Ji H, Chen X, Zhao Y, Zhao D, Li N, Zhang LAssessment of UDP-glucuronosyltransferase catalyzed formation of Picroside II glucuronide in microsomes of different species and recombinant UGTsXenobiotica.(2011 Jul)
- ^Lee HS, Yoo CB, Ku SKHypolipemic effect of water extracts of Picrorrhiza kurroa in high fat diet treated mouseFitoterapia.(2006 Dec)
- ^Lee HS, Ahn HC, Ku SKHypolipemic effect of water extracts of Picrorrhiza rhizoma in PX-407 induced hyperlipemic ICR mouse model with hepatoprotective effects: a prevention studyJ Ethnopharmacol.(2006 May 24)
- ^Husain GM, Singh PN, Kumar VAntidiabetic activity of standardized extract of Picrorhiza kurroa in rat model of NIDDMDrug Discov Ther.(2009 Jun)
- ^Simons JM, Hart BA, Ip Vai Ching TR, Van Dijk H, Labadie RPMetabolic activation of natural phenols into selective oxidative burst agonists by activated human neutrophilsFree Radic Biol Med.(1990)
- ^Gao HM, Liu B, Zhang W, Hong JSCritical role of microglial NADPH oxidase-derived free radicals in the in vitro MPTP model of Parkinson's diseaseFASEB J.(2003 Oct)
- ^Chamorro G, Pérez-Albiter M, Serrano-García N, Mares-Sámano JJ, Rojas PSpirulina maxima pretreatment partially protects against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine neurotoxicityNutr Neurosci.(2006 Oct-Dec)
- ^Hussain A, Shadma W, Maksood A, Ansari SHProtective effects of Picrorhiza kurroa on cyclophosphamide-induced immunosuppression in micePharmacognosy Res.(2013 Jan)
- ^Dorsch W, Wagner HNew antiasthmatic drugs from traditional medicineInt Arch Allergy Appl Immunol.(1991)
- ^Thomas M, Sheran J, Smith N, Fonseca S, Lee AJAKL1, a botanical mixture for the treatment of asthma: a randomised, double-blind, placebo-controlled, cross-over studyBMC Pulm Med.(2007 Mar 20)
- ^Antarkar DS, Vaidya AB, Doshi JC, Athavale AV, Vinchoo KS, Natekar MR, Tathed PS, Ramesh V, Kale NA double-blind clinical trial of Arogya-wardhani--an ayurvedic drug--in acute viral hepatitisIndian J Med Res.(1980 Oct)
- ^Rastogi R, Srivastava AK, Rastogi AKBiochemical changes induced in liver and serum of aflatoxin B1-treated male wistar rats: preventive effect of picrolivPharmacol Toxicol.(2001 Feb)
- ^Rastogi R, Srivastava AK, Srivastava M, Rastogi AKHepatocurative effect of picroliv and silymarin against aflatoxin B1 induced hepatotoxicity in ratsPlanta Med.(2000 Dec)
- ^Dwivedi Y, Rastogi R, Mehrotra R, Garg NK, Dhawan BNPicroliv protects against aflatoxin B1 acute hepatotoxicity in ratsPharmacol Res.(1993 Feb-Mar)
- ^Saraswat B, Visen PK, Patnaik GK, Dhawan BNProtective effect of picroliv, active constituent of Picrorhiza kurrooa, against oxytetracycline induced hepatic damageIndian J Exp Biol.(1997 Dec)
- ^Santra A, Das S, Maity A, Rao SB, Mazumder DNPrevention of carbon tetrachloride-induced hepatic injury in mice by Picrorhiza kurrooaIndian J Gastroenterol.(1998 Jan)
- ^Girish C, Pradhan SCHepatoprotective activities of picroliv, curcumin, and ellagic acid compared to silymarin on carbon-tetrachloride-induced liver toxicity in miceJ Pharmacol Pharmacother.(2012 Apr)
- ^Dwivedi Y, Rastogi R, Sharma SK, Garg NK, Dhawan BNPicroliv affords protection against thioacetamide-induced hepatic damage in ratsPlanta Med.(1991 Feb)
- ^Girish C, Koner BC, Jayanthi S, Ramachandra Rao K, Rajesh B, Pradhan SCHepatoprotective activity of picroliv, curcumin and ellagic acid compared to silymarin on paracetamol induced liver toxicity in miceFundam Clin Pharmacol.(2009 Dec)
- ^Shukla B, Visen PK, Patnaik GK, Dhawan BNCholeretic effect of picroliv, the hepatoprotective principle of Picrorhiza kurroaPlanta Med.(1991 Feb)
- ^Yadav N, Khandelwal SEffect of Picroliv on cadmium-induced hepatic and renal damage in the ratHum Exp Toxicol.(2006 Oct)
- ^Yadav N, Khandelwal STherapeutic efficacy of Picroliv in chronic cadmium toxicityFood Chem Toxicol.(2009 Apr)
- ^Singh AK, Mani H, Seth P, Gaddipati JP, Kumari R, Banuadha KK, Sharma SC, Kulshreshtha DK, Maheshwari RKPicroliv preconditioning protects the rat liver against ischemia-reperfusion injuryEur J Pharmacol.(2000 May 3)
- ^Effect of picroliv on antioxidant-system in liver of rats, after partial hepatectomy
- ^Dwivedi Y, Rastogi R, Sharma SK, Mehrotra R, Garg NK, Dhawan BNPicroliv protects against monocrotaline-induced hepatic damage in ratsPharmacol Res.(1991 May)
- ^Vivekanandan P, Gobianand K, Priya S, Vijayalakshmi P, Karthikeyan SProtective effect of picroliv against hydrazine-induced hyperlipidemia and hepatic steatosis in ratsDrug Chem Toxicol.(2007)
- ^Dwivedi Y, Rastogi R, Garg NK, Dhawan BNPicroliv and its components kutkoside and picroside I protect liver against galactosamine-induced damage in ratsPharmacol Toxicol.(1992 Nov)
- ^Rastogi R, Saksena S, Garg NK, Kapoor NK, Agarwal DP, Dhawan BNPicroliv protects against alcohol-induced chronic hepatotoxicity in ratsPlanta Med.(1996 Jun)
- ^Floersheim GL, Bieri A, Koenig R, Pletscher AProtection against Amanita phalloides by the iridoid glycoside mixture of Picrorhiza kurroa (kutkin)Agents Actions.(1990 Mar)
- ^Saraswat B, Visen PK, Patnaik GK, Dhawan BNEx vivo and in vivo investigations of picroliv from Picrorhiza kurroa in an alcohol intoxication model in ratsJ Ethnopharmacol.(1999 Sep)
- ^Saraswat B, Visen PK, Patnaik GK, Dhawan BNAnticholestatic effect of picroliv, active hepatoprotective principle of Picrorhiza kurrooa, against carbon tetrachloride induced cholestasisIndian J Exp Biol.(1993 Apr)
- ^Shetty SN, Mengi S, Vaidya R, Vaidya ADA study of standardized extracts of Picrorhiza kurroa Royle ex Benth in experimental nonalcoholic fatty liver diseaseJ Ayurveda Integr Med.(2010 Jul)
- ^Rogler G, Andus TCytokines in inflammatory bowel diseaseWorld J Surg.(1998 Apr)
- ^Ogata H, Hibi TCytokine and anti-cytokine therapies for inflammatory bowel diseaseCurr Pharm Des.(2003)
- ^Xiang JY, Wu LG, Huang XL, Zhang M, Pen L, Ouyan Q, Gan HTAmelioration of murine dextran sulfate sodium-induced colitis by nuclear factor-kappaB decoy oligonucleotidesAm J Surg.(2009 Jun)
- ^Jobin C, Sartor RBNF-kappaB signaling proteins as therapeutic targets for inflammatory bowel diseasesInflamm Bowel Dis.(2000 Aug)
- ^Yadav N, Khandelwal SEffect of Picroliv on cadmium induced testicular damage in ratFood Chem Toxicol.(2008 Feb)
- ^Yadav N, Dogra RK, Khan MY, Khandelwal SPrevention of acute cadmium toxicity by PicrolivHum Exp Toxicol.(2005 Oct)
- ^Bedi KL, Zutshi U, Chopra CL, Amla VPicrorhiza kurroa, an ayurvedic herb, may potentiate photochemotherapy in vitiligoJ Ethnopharmacol.(1989 Dec)