Articles

Picrorhiza

Plant Part Used

Root/rhizome

Active Constituents

Iridoid glycosides (including picroside I, II, III, pikuroside, kutkoside and 6-feruloyl catalpol), cucurbitacin glycosides, androsin, apocynin.(1),(2)

[span class=alert]This section is a list of chemical entities identified in this dietary supplement to possess pharmacological activity. This list does not imply that other, yet unidentified, constituents do not influence the pharmacological activity of this dietary supplement nor does it imply that any one constituent possesses greater influence on the overall pharmacological effect of this dietary supplement.[/span]

Introduction

Picrorhiza is a perennial herb that grows in the Himalayas in Asia, at altitudes of 9,000-15,000 feet above sea level. The underground parts of this plant have been used in the traditional Indian (Ayurvedic) systems of medicine since ancient times to treat liver and bronchial problems. Picrorhiza has also been used traditionally to treat the lungs as well as infectious diseases, reduce fevers, and alleviate indigestion. Researchers and clinicians have reported the value of picrorhiza as an immune-enhancing and hepatoprotective agent.(30)

Several biologically active principles, particularly glycosides, have been identified in extracts obtained from picrorhiza. Of these, a mixture of the iridoid glycosides, picroside I, and kutkoside has been found to be an efficient liver protectant. Androsin, a phenolic glycoside isolated from picrorhiza, has been attributed with anti-asthmatic properties.(3) Picrorhiza has also been used in India with success for the treatment of vitiligo.(4)

Interactions and Depletions

Interactions

Dosage Info

Dosage Range

250mg (standardized extract), 2 to 4 times daily.

Tincture: 2 to 4 ml daily.(5)

Most Common Dosage

250mg (standardized extract), 2 times daily.

Tincture: 2 ml daily.

Standardization

[span class=doc]Standardization represents the complete body of information and controls that serve to enhance the batch to batch consistency of a botanical product, including but not limited to the presence of a marker compound at a defined level or within a defined range.[/span]

The most current available medical and scientific literature indicates that this dietary supplement should be standardized to 4%-10% kutkin.

Uses

Frequently Reported Uses

    • Hepatoprotective Against Psychotropics And Other Pharmaceuticals
    • Hepatitis (Acute, Chronic)
    • Hepatoprotective

      Other Reported Uses

        • Allergies
        • Asthma
        • Antioxidant
        • Hypoxia
        • Anti-Inflammatory.
        • Increases Cellular Oxygenation
        • Vitiligo
        • Immune Enhancing

          Toxicities & Precautions

          General

          Picrorhiza is reported safe in recommended dosages.

          Health Conditions

          Based on pharmacology, use with caution in individuals with bleeding disorders.

          Side Effects

          Only transient side effects such as mild nausea and gastrointestinal upset have been reported.

          Pregnancy/ Breast Feeding

          If pregnant or nursing, consult a physician before use.

          Age Limitations

          Do not use in children under 2 years of age unless recommended by a physician.

          Pharmacology

          Hepato-protection.

          Similar to milk thistle, picrorhiza may have an effect on liver regeneration. A 1992 study demonstrated stimulation of nucleic acid and protein synthesis in rat liver with oral administration of picrorhiza. The authors stated the results were comparable to milk thistle.(6)

          There have been over 15 studies conducted in laboratory animals regarding the effectiveness of standardized picrorhiza as a tool in liver health. Studies report picrorhiza beneficial for the liver, including viral hepatitis, and exposure to hepatotoxic chemical agents, including alcohol and acetaminophen.(7),(8),(9),(10) Another factor in the hepato-protection of picrorhiza may be its anti-inflammatory effects.

          Picrorhiza was evaluated as a hepato-protective agent against ethanol-induced hepatic injury in rats.(11) There was also an effect on specific alcohol-metabolizing enzymes (aldehyde dehydrogenase, 41%; acetaldehyde dehydrogenase, 52%) in rat hepatocytes. The levels of these enzymes were found to be reduced in the cells following alcohol intoxication.

          Several hepatotoxins, including paracetamol and ethynyl estradiol, have a cholestatic effect on the production of bile.

          Picrorhiza has been reported to reverse acetaminophen and ethynyl estradiol-induced cholestasis, maintaining both bile volume and flow. Milk thistle was tested simultaneously for comparison. Picrorhiza was found to be a more potent choleretic and anticholestatic agent than milk thistle.(12) Ethyl alcohol also produces cholestasis to varying degrees, as indicated by reduction in bile volume, bile salts, and bile acids. Picrorhiza treatment has been reported to restore these altered parameters in a dose-dependent manner.(11)

          In a randomized, double-blind placebo controlled trial in patients diagnosed to have acute viral hepatitis (HBsAg negative), picrorhiza root powder, 375mg three times a day, was given for two weeks.(9) Picrorhiza was reported to significantly decrease lab values of bilirubin, SGOT, and SGPT as compared to placebo. The time in days required for total serum bilirubin to drop to an average value of 2.5mg% was 75.9 days in placebo compared to 27.44 days in the picrorhiza group. Also, the active principles picroside I, catalpol, kutkoside, and kutkoside 1 were tested for the presence of anti-hepatitis B virus surface antigen (anti-HBsAg) like activity in vitro.(13) A promising anti-HBsAg like activity was noted which differed from the classical viral neutralization. Picrorhiza also inhibited purified HBV antigens prepared from healthy HBsAg carriers from binding in vitro.

          As an antioxidant for the liver, picrorhiza is reported to protect against changes in liver and brain glutathione metabolism, improving reduced glutathione levels, and decreasing inhibition of glutathione-S-transferase, glutathione reductase, and glutathione peroxidase.(14) The increased levels of lipid peroxidation products in damaged tissues were also reduced along with the recovery of glutathione metabolism. Also, picrorhiza possess the properties of antioxidants that appear to be mediated through activity like that of superoxide dismutase, metal ion chelators, and xanthine oxidase inhibitors.(15) Picrorhiza does seem to alter cytochrome P-450 enzyme levels. Therefore, caution should be used with medications that are metabolized in the liver.(16) A laboratory study found that picrorhiza decreased the hepatotoxic effects of cadmium.(32)

          Asthma

          Several studies have reported benefit in patients with asthma when using picrorhiza. In a randomized crossover study using laboratory animals, administration of isolated androsin orally or by inhalation prevented bronchial obstruction induced by the inhalation of allergens, platelet activity factors (PAF), histamine, and acetylcholine.(17) It was concluded in this study that asthmatic reactions due to histamine and acetylcholine were not altered by picrorhiza, suggesting that androsin is not a broncholytic agent, but prevents bronchial obstruction. It is suggested that androsin may act by depressing the activity of PAF, which plays a major role in the pathogenesis of bronchial asthma. PAF has been reported to provoke long-term inflammatory responses in the lungs, leading to bronchial hyper-reactivity and subsequent bronchial obstruction. Additionally, histamine release from human polymorphonuclear leucocytes, in vitro, has been reported inhibited by some compounds from picrorhiza that have yet to be identified.(18) Picrorhiza reportedly stabilizes mast cells in vivo, further elucidated by a repeated study in vitro in laboratory animals.(19),(20) This may prove useful as part of an integrative approach in patients with allergic conditions.

          A one-year clinical study of 20 patients (ages 14-60 years), two with perennial asthma, others with seasonal asthma, was conducted using picrorhiza as a therapeutic agent.(21) The degree of clinical improvement in the patients was measured in terms of reduction in the use of bronchodilators, as evident from the results of pulmonary function tests at regular intervals. The patients had experienced asthma symptoms ranging from five to twenty years. The peak expiratory flow rate (PEFR) was monitored and reported sustained increases for up to twelve months of treatment with picrorhiza. The frequency and severity of asthmatic attacks reduced significantly as treatment progressed. A reduction in bronchodilator use was also observed. One observation of interest is that individuals having specific food allergies developed tolerance to these allergens during the period of treatment, probably due in part to the mast cell stabilization properties of picrorhiza.

          A double-blind, crossover trial with placebo failed to demonstrate significant results, although there was a trend toward improvement in symptoms of asthma.(22) Study design and high dropout rate in this trial may have contributed to the poor results.

          Inflammation

          Apocynin is a constituent of root extracts of picrorhiza and has been reported to possess anti-inflammatory properties in laboratory animals.(23) Apocynin concentration dependently inhibited the formation of thromboxane A2, whereas the release of prostaglandins E2 and F2 alpha was stimulated. Apocynin inhibited arachidonic acid-induced aggregation of bovine platelets, possibly through inhibition of thromboxane formation. Apocynin was found to inhibit neutrophil oxidative burst in vitro without affecting beneficial activities such as chemotaxis, phagocytosis, and intracellular killing of bacteria.(24)

          Other Uses

          Hypoglycemic. An extract of picrorhiza was found to lower blood glucose in laboratory animals.(25) Chronic administration of the extract significantly reduced blood sugar in alloxan-induced diabetic rats for 10 days. The extract was also found to reduce the increased blood urea nitrogen and serum lipid peroxides in alloxan-induced diabetic animals and to inhibit the body weight reduction and leukopenia induced by alloxan administration. Further study is required to determine benefits to diabetics.

          Immune system modulation. The effect of an ethanolic extract of each drug was studied on delayed type, hypersensitivity, humoral responses to sheep red blood cells, skin allograft rejection, and phagocytic activity of the reticuloendothelial system in mice. Picrorhiza kurroa was found to be a potent immunostimulant of both cell-mediated and humoral immunity.(26) The clinical success in treating vitiligo, a benign autoimmune disease characterized by irregular skin patches without pigmentation, is attributed to the immunomodulating effects of picrorhiza.

          Recently, an ethanolic extract of the leaf of picrorhiza was reported to stimulate cell mediated and humoral components of the immune system including stimulation of phagocytosis.(27) Also, picrorhiza root has reported anti-tumour and anti-carcinogenic activity in laboratory studies.(28)

          Hypoxia Picrorhiza has been reported to protect cells and regulate gene expression during hypoxia and/or re-oxygenation.(29) Picrorhiza reduced the cellular damage caused by hypoxia as revealed by a significant reduction in LDH release compared to untreated controls. These findings suggest that picrorhiza may act as a protective agent against hypoxia and/or re-oxygenation induced injuries by a novel signal transduction pathway to the cells.

          Lipid Lowering. A laboratory animal study found that picrorhiza decreased total cholesterol, LDL and triglycerides in hyperlipidemic rats.(32)

          References

          1. Vanhaelen M, et al. Quantitative Determination of Biologically Active Constituents in Crude Extracts of Medicinal Plants by Thin-layer Chromatography-densitometry. II. Eleutherococcus senticosus Maxim., Panax ginseng Meyer and Picrorrhiza kurroa Royle. J Chromatogr. Nov1984;312:497-503.
          2. View Abstract: Jia Q, et al. Pikuroside: A Novel Iridoid from Picrorhiza kurroa. J Nat Prod. Jun1999;62(6):901-03.
          3. View Abstract: Dorsch W, et al. New Antiasthmatic Drugs from Traditional Medicine? Int Arch Allergy Appl Immunol. 1991;94(1-4):262-65.
          4. Bedi KL, et al. Picrorhiza kurroa, An Aurvedic Herb, May Potentiate Photochemotherapy in Vitiligo. J Ethnopharmacol. Dec1989;27(3):347-52.
          5. PDR for Herbal Medicines, 2nd edition. Montvale, NJ: Medical Economics Company; 2000:590.
          6. View Abstract: Singh V, et al. Effect of Picroliv on Protein and Nucleic Acid Synthesis. Indian J Exp Biol. Jan1992;30(1):68-69.
          7. View Abstract: Visen PK, et al. Curative Effect of Picroliv on Primary cultured Rat Hepatocytes Against Different Hepatotoxins: An In Vitro Study. J Pharmacol Toxicol Methods. Oct1998;40(3):173-79.
          8. View Abstract: Santra A, et al. Prevention of Carbon Tetrachloride-induced Hepatic Injury in Mice by Picrorhiza kurrooa. Indian J Gastroenterol. Jan1998;17(1):6-9.
          9. View Abstract: Vaidya AB, et al. Picrorhiza kurroa (Kutaki) Royle ex Benth As a Hepatoprotective Agent--Experimental and Clinical Studies. J Postgrad Med. Dec1996;42(4):105-08.
          10. View Abstract: Rastogi R, et al. Picroliv Protects Against Alcohol-induced Chronic Hepatotoxicity in Rats. Planta Med. Jun1996;62(3):283-85.
          11. View Abstract: Saraswat B, et al. Ex Vivo and In Vivo Investigations of Picroliv from Picrorhiza kurroa in An Alcohol Intoxication Model in Rats. J Ethnopharmacol. Sep1999;66(3):263-69.
          12. View Abstract: Shukla B, et al. Choleretic Effect of Picroliv, The Hepatoprotective Principle of Picrorhiza kurroa. Planta Med. Feb1991;57(1):29-33.
          13. View Abstract: Mehrotra R, et al. In Vitro Studies on the Effect of Certain Natural Products Against Hepatitis B Virus. Indian J Med Res. Apr1990;92:133-38.
          14. View Abstract: Chander R, et al. Effect of Picroliv on Glutathione Metabolism in Liver and Brain of Mastomys natalensis Infected with Plasmodium berghei. Indian J Exp Biol. Aug1992;30(8):711-14.
          15. View Abstract: Chander R, et al. Picroliv, Picroside-I and Kutkoside from Picrorhiza kurrooa are Scavengers of Superoxide Anions. Biochem Pharmacol. Jul1992;44(1):180-83.
          16. View Abstract: Dwivedi Y, et al. Picroliv Protects Against Aflatoxin B1 Acute Hepatotoxicity in Rats. Pharmacol Res. Feb1993;27(2):189-99.
          17. View Abstract: Dorsch W, et al. Antiasthmatic Effects of Picrorhiza kurroa: Androsin Prevents Allergen- and PAF-Induced Bronchial Obstruction in Guinea Pigs. Int Arch Allergy Appl Immunol. 1991;95(2-3):128-33.
          18. Langer JG, et al. Clinical Trials on Picrorhiza kurroa. Ind J Pharmacol. 1981;13:98-103.
          19. Pandey BL, et al. Immunopharmacological Studies on Picrorrhiza kurroa Royale Ex Benth Part II: Antiallergic Activity. Ind J Allergy Applied Immunol. 1988;2:21-34.
          20. View Abstract: Panley BL, et al. Immunopharmacological Studies on Picrorrhiza kurroa Royale Ex Benth Par VI: Effect on Anaphylactic Activation Events in Rat Peritoneal Mast Cells. Ind J Physiol Pharmacol. 1989;33:47-52.
          21. Yegnanarayanan R, et al. Study of Picrorhiza kurroa (PK 300) in Cases of Bronchial Asthma. Bombay Hos J. 1982;24(2):15-18.
          22. Doshi VB, et al. Picrorrhiza kurroa in Bronchial Asthma. J Postgrad Med. 1983;29:89-95.
          23. View Abstract: Engels F, et al. Effects of Apocynin, A Drug Isolated from the Roots of Picrorhiza kurroa, on Arachidonic Acid Metabolism. FEBS Lett. Jul1992;305(3):254-56.
          24. View Abstract: Simons JM, et al. Metabolic Activation of Natural Phenols into Selective Oxidative Burst Agonists by Activated Human Neutrophils. Free Radic Biol Med. 1990;8(3):251-58.
          25. View Abstract: Joy KL, et al. Anti-diabetic Activity of Picrorrhiza kurroa extract. J Ethnopharmacology. Nov1999;67(2):143-148.
          26. View Abstract: Atal CK, et al. Immunomodulating Agents of Plant Origin. I: Preliminary Screening. J Ethnopharmacol. Nov1986;18(2):133-41.
          27. View Abstract: Sharma ML, et al. Immunostimulatory Activity of Picrorhiza kurroa Leaf Extract. J Ethnopharmacol. Feb1994;41(3):185-92.
          28. View Abstract: Joy KL, Rajeshkumar NV, Kuttan G, et al. Effect of Picrorrhiza kurroa Extract on Transplanted Tumours and Chemical Carcinogenesis in Mice. J Ethnopharmacol. Jul2000;71(1-2):261-6.
          29. View Abstract: Gaddipati JP, et al. Picroliv -- A Natural Product Protects Cells and Regulates the Gene Expression During Hypoxia/Reoxygenation. Mol Cell Biochem. Apr1999;194(1-2):271-81.
          30. Verma PC, Basu V, Gupta V, Saxena G, Rahman LU. Pharmacology and chemistry of a potent hepatoprotective compound Picroliv isolated from the roots and rhizomes of Picrorhiza kurroa royle ex benth. (kutki). Curr Pharm Biotechnol. Sep 2009;10(6):641-649. Review.
          31. Yadav N, Khandelwal S. Therapeutic Efficacy of Picroliv in Chronic Cadmium Toxicity. Food Chem Toxicol. 20 Jan 2009. [Epub ahead of print]
          32. Lee HS, Yoo CB, Ku SK. Hypolipemic effect of water extracts of Picrorrhiza kurroa in high fat diet treated mouse. Fitoterapia. Dec 2006;77(7-8):579-584. Epub 2006 Sep 22.