My milk thistle research on PubMed

  1. My milk thistle research on PubMed

    Am J Gastroenterol. 1998 Feb;93(2):139-43. Related Articles, Links
    Comment in:
    Milk thistle (Silybum marianum) for the therapy of liver disease.

    Flora K, Hahn M, Rosen H, Benner K.

    Division of Gastroenterology, Oregon Health Sciences University, Portland 97201-3098, USA.

    Silymarin, derived from the milk thistle plant, Silybum marianum, has been used for centuries as a natural remedy for diseases of the liver and biliary tract. As interest in alternative therapy has emerged in the United States, gastroenterologists have encountered increasing numbers of patients taking silymarin with little understanding of its purported properties. Silymarin and its active constituent, silybin, have been reported to work as antioxidants scavenging free radicals and inhibiting lipid peroxidation. Studies also suggest that they protect against genomic injury, increase hepatocyte protein synthesis, decrease the activity of tumor promoters, stabilize mast cells, chelate iron, and slow calcium metabolism. In this article we review silymarin's history, pharmacology, and properties, and the clinical trials pertaining to patients with acute and chronic liver disease.

    Publication Types:PMID: 9468229 [PubMed - indexed for MEDLINE]

    Silymarin retards the progression of alcohol-induced hepatic fibrosis in baboons.

    Lieber CS, Leo MA, Cao Q, Ren C, DeCarli LM.

    Section of Liver Disease & Nutrition, Bronx VA Medical Center & Mount Sinai School of Medicine, Bronx, New York 10468, USA. [email protected]

    GOAL/BACKGROUND: Hepatoprotective effects of silymarin in patients with alcoholic liver disease are controversial. For strict control, this was assessed in non-human primates.STUDY Twelve baboons were fed alcohol with or without silymarin for 3 years with a nutritionally adequate diet. RESULTS: Silymarin opposed the alcohol-induced oxidative stress (assessed by plasma 4-hydroxynonenal) and the rise in liver lipids and circulating ALT. Alcohol also increased hepatic collagen type I by 50% over the 3 years with a significant rise in mRNA for alpha1 (I) procollagen, both prevented by silymarin. There were corresponding morphologic changes: at 36 months, 2 of 6 animals fed alcohol had cirrhosis and 2 septal fibrosis, with perivenular fibrosis in 2, whereas with alcohol + silymarin, there was only 1 cirrhosis and 1 septal fibrosis, with perivenular fibrosis in 2, and virtually no lesions in the remaining 2. CONCLUSIONS: Silymarin retards the development of alcohol-induced hepatic fibrosis in baboons, consistent with several positive clinical trials. The negative outcome observed in other trials possibly reflects poor compliance resulting in irregular or low silymarin intake. Thus, in view of the innocuity of silymarin, it might be advisable in future clinical studies to insure the controlled administration of sufficient amounts of silymarin.

    Effect of silybin and its congeners on human liver microsomal cytochrome P450 activities.

    Zuber R, Modriansky M, Dvorak Z, Rohovsky P, Ulrichova J, Simanek V, Anzenbacher P.

    Faculty of Chemical Technology, University of Pardubice, Nam. Cs. Legii 565, 532 10 Pardubice, Czech Republic.

    Silybin and related flavonolignans form a major part of the Silybum marianum extract, silymarin, which has been used to treat liver diseases for hundreds of years. Although regarded as safe, many of the extract constituents remain thus far untested for their possible effects on liver biotransformation enzymes. Cytochromes P450 (CYP) are very important in this regard. We tested the effect of four flavonolignans: silybin, its hemisynthetic derivative dehydrosilybin, silydianin, and silycristin on three specific CYP activities: bufuralol 1'-hydroxylation (CYP2D6), p-nitrophenol hydroxylation (CYP2E1), and nifedipine oxidation (CYP3A4). All flavonolignans displayed dose-dependent inhibition of these activities with IC(50) values in the micromolar range. The inhibition was competitive or mixed as revealed by double reciprocal plots of kinetic experiments. However, the inhibition is not considered to be relevant for therapy because physiological concentrations of the individual flavonolignans do not exceed 0.5 microM. The data support the use of the extract as a dietary supplement. Copyright 2002 John Wiley & Sons, Ltd.

    PMID: 12410543 [PubMed - indexed for MEDLINE]

    The use of silymarin in the treatment of liver diseases.

    Saller R, Meier R, Brignoli R.

    Abteilung Naturheilkunde, University Hospital Zurich, Switzerland.

    The high prevalence of liver diseases such as chronic hepatitis and cirrhosis underscores the need for efficient and cost-effective treatments. The potential benefit of silymarin (extracted from the seeds of Silybum marianum or milk thistle) in the treatment of liver diseases remains a controversial issue. Therefore, the objective of this review is to assess the clinical efficacy and safety of silymarin by application of systematic approach. 525 references were found in the databases, of which 84 papers were retained for closer examination and 36 were deemed suitable for detailed analysis. Silymarin has metabolic and cell-regulating effects at concentrations found in clinical conditions, namely carrier-mediated regulation of cell membrane permeability, inhibition of the 5-lipoxygenase pathway, scavenging of reactive oxygen species (ROS) of the R-OH type and action on DNA-expression, for example, via suppression of nuclear factor (NF)-kappaB. Pooled data from case record studies involving 452 patients with Amanita phalloides poisoning show a highly significant difference in mortality in favour of silibinin [the main isomer contained in silymarin] (mortality 9.8% vs 18.3% with standard treatment; p < 0.01). The available trials in patients with toxic (e.g. solvents) or iatrogenic (e.g. antispychotic or tacrine) liver diseases, which are mostly outdated and underpowered, do not enable any valid conclusions to be drawn on the value of silymarin. The exception is an improved clinical tolerance of tacrine. In spite of some positive results in patients with acute viral hepatitis, no formally valid conclusion can be drawn regarding the value of silymarin in the treatment of these infections. Although there were no clinical end-points in the four trials considered in patients with alcoholic liver disease, histological findings were reported as improved in two out of two trials, improvement of prothrombin time was significant (two trials pooled) and liver transaminase levels were consistently lower in the silymarin-treated groups. Therefore, silymarin may be of use as an adjuvant in the therapy of alcoholic liver disease. Analysis was performed on five trials with a total of 602 patients with liver cirrhosis. The evidence shows that, compared with placebo, silymarin produces a nonsignificant reduction of total mortality by -4.2% [odds ratio (OR) 0.75 (0.5 - 1.1)]; but that, on the other hand, the use of silymarin leads to a significant reduction in liver-related mortality of-7% [OR: 0.54 (0.3 - 0.9); p < 0.01]. An individual trial reported a reduction in the number of patients with encephalopathy of -8.7% (p = 0.06). In one study of patients with cirrhosis-related diabetes mellitus, the insulin requirement was reduced by -25% (p < 0.01). We conclude that available evidence suggests that silymarin may play a role in the therapy of (alcoholic) liver cirrhosis. Silymarin is has a good safety record and only rare case reports of gastrointestinal disturbances and allergic skin rashes have been published. This review does not aim to replace future prospective trials aiming to provide the 'final' evidence of the efficacy of silymarin.

    Publication Types:PMID: 11735632 [PubMed - indexed for MEDLINE]

    New treatments for hepatitis B and C [antigen-specific transfer for A, B & C (chisolm biologicals) and thymate].

    Konlee M.

    AIDS: Millions of people in this country are infected with Hepatitis C; however, long-term treatment for this disease is not always successful. Chisolm Biologicals produces a transfer factor panel for hepatitis A, B, and C that appears to be effective in treating hepatitis. Other products, including Thy-Mate and Liver Support, may also help treat hepatitis. Patients with hepatitis should tell their doctor what products they are using and have their physicians monitor liver enzyme levels and viral loads. One study of 24 patients showed success in using Naltrexone, Alpha Lipoic acid, milk thistle, and Hypercurium in treating hepatitis B and C. Contact information is included.

    Publication Types:PMID: 11366548 [PubMed - indexed for MEDLINE]

    Altern Med Rev. 1998 Dec;3(6):410-21. Related Articles, Links
    A review of plants used in the treatment of liver disease: part 1.

    Luper S.

    Southwest College of Naturopathic Medicine: 2140 East Broadway Rd. Tempe, AZ 85282, USA. [email protected]

    Botanicals have been used traditionally by herbalists and indigenous healers worldwide for the prevention and treatment of liver disease. Clinical research in this century has confirmed the efficacy of several plants in the treatment of liver disease. Basic scientific research has uncovered the mechanisms by which some plants afford their therapeutic effects. Silybum marianum (milk thistle) has been shown to have clinical applications in the treatment of toxic hepatitis, fatty liver, cirrhosis, ischemic injury, radiation toxicity, and viral hepatitis via its antioxidative, anti-lipid peroxidative, antifibrotic, anti-inflammatory, immunomodulating, and liver regenerating effects. Picrorhiza kurroa, though less well researched than Silybum, appears to have similar applications and mechanisms of action. When compared with Silybum, the hepatoprotective effect of Picrorhiza was found to be similar, or in many cases, superior to the effect of Silybum.

    Publication Types:

    PMID: 9855566 [PubMed - indexed for MEDLINE]
    Altern Med Rev. 1999 Jun;4(3):178-88. Related Articles, Links
    A review of plants used in the treatment of liver disease: part two.

    Luper S.

    Southwest College of Naturopathic Medicine: 2140 East Broadway Rd. Tempe, AZ 85282, USA. [email protected]

    Botanical medicines have been used traditionally by herbalists and indigenous healers worldwide for the prevention and treatment of liver disease. Clinical research in this century has confirmed the efficacy of several plants in the treatment of liver disease, while basic scientific research has uncovered the mechanisms by which some plants provide their therapeutic effects. This article is Part Two in a review of botanicals used in the treatment of liver disease. Curcuma longa (turmeric), Camellia sinensis (green tea), and Glycyrrhiza glabra (licorice) are reviewed in this installment. Silybum marianum (milk thistle) and Picrorhiza kurroa (kutkin) were reviewed in Part One.

    Publication Types:

    PMID: 10383482 [PubMed - indexed for MEDLINE]

    The 2 last ones (in italics) would be VERY nice to get a hold of, just to extract the conclusions on Milk Thistle...

  2. Good info - A Summation perhaps?

  3. I've been reviewing some articles which note that if milk thistle is combined with phosphatidylcholine, then milk thistle has more then 3 x the oral bioavailability and efficacy... Anyone else hear the same??

  4. For a summation, well, the first (link) is pretty good. Hey I gotta stop posting all this info, my rep is going straight down. Is there an auto-ban at some point?

    The gospel is only to be spread by Holy Priests?

  5. Talk about some negative reps! -41?

    A summary would have been nice or keypoints in the abstracts.

    Good job though practicing your copy and paste skills!

  6. Hey I had to read through all the extracts to find the ones that are more relevant to us BBers.

    Now I've even highlighted the good parts. And my rep had improved even BEFORE that.

    Does milk thistle increase hepatic clearance of drugs?

    Townsend Letter for Doctors and Patients, August-Sept, 2005 by Kerry Bone

    A common misconception concerning milk thistle (Silybum marianum) is that, since it is a liver herb, it is likely to increase the metabolism and clearance of many drugs due to enhanced hepatic detoxification. This is certainly fueled by in vitro studies showing this effect (1) and an in vivo study in rats where high doses increased phase I hepatic metabolism. Oral administration of silymarin (100 mg/kg/day) to rats resulted in a significant increase in the activity of the mixed-function oxidation system (cytochrome P450; aminopyrine demethylation, p-nitroanisole demethylation). However, an experimentally-induced reduction in activities of the mixed-function oxidation system and glucose-6-phosphatase could not be prevented by pretreatment with silymarin.
    In human volunteers, treatment with silymarin (210 mg/day for 28 days) had no influence on the metabolism of aminopyrine or phenylbutazone. (2) Concentrated milk thistle (silymarin) extract at commonly administered doses did not interfere with indinavir therapy in patients with HIV. (3) In other words, despite the findings of in vitro and in vivo studies, there was no evidence from clinical studies that milk thistle extract increases phase I/II liver metabolism. The reason behind this discrepancy is probably that normal clinical doses are not high enough to achieve the effects shown at the artificially high doses used in experimental models.
    But a study has recently been published which, on the face of it, appears to challenge this position. (4) A clinical study was undertaken in 12 healthy volunteers. At first, subjects received metronidazole (Flagyl; a substrate for cytochrome CYP3A4 and CYP2C9) alone at a dose of 400 mg every 8 h for 3 days. On day 4, blood and urine were collected at different time points and metronidazole levels were measured. After a washout period of one week silymarin was given at a daily dose of 140 mg for 9 days. From day 7 both silymarin (140 mg/day) and metronidazole (3 X 400 mg/day) were given till the 9th day. On day 10, blood and urine were collected as above and the levels of metronidazole and its metabolite were measured. Administration of silymarin increased the clearance of metronidazole and its major metabolite, hydroxy-metronidazole (HM) by 29.51% and 31.90% respectively, with a concomitant decrease in half-life and maximum concentration. Urinary excretions of acid-metronidazole, HM and metronidazole were all decreased.

    The key to understanding this recent study is the decreased levels of metronidazole and its metabolites in serum and urine. This suggests reduced absorption into the bloodstream via the induction of the drug transporting P-glycoprotein (P-gp), particularly at the level of the intestine. P-gp is a molecule that acts as a drug efflux pump at epithelial cells, especially the intestinal wall. In other words, induction of P-gp results in less absorption of any drug which is subject to its effects. So the most likely explanation of the findings is a reduced uptake due to P-gp induction, rather than increased clearance resulting from the induction of hepatic phase I cytochrome P450 enzymes such as CYP 3A4. Nonetheless, it is possible that silymarin could reduce the oral bioavailability of other drugs susceptible to P-gp, which include paclitaxel and digoxin.

    1. Mills S, Bone K. Principles and Practice of Phytotherapy: Modern Herbal Medicine. Churchill Livingstone, Edinburgh, 2000, pp 556-557.
    2. Leber HW, Knauff S. Arzneim-Forsch 1976; 26(8): 1603-1605
    3. Piscitelli SC, Formentini E, Burstein AH et al. Pharmacotherapy 2002; 22(5): 551-556
    4. Rajnarayana K, Reddy MS, Vidyasagar J et al. Arzneim-Forsch 2004; 54(2): 109-113


    Oh, and here on Picrorhiza kurroa:

    Picrorhiza kurroa (Pk), a known hepatoprotective plant, was studied in experimental and clinical situtations. The standardization of active principles--Picroside 1 and 2 was done with High Performance Liquid Chromatography. Picroside 1 ranged from 2.72 to 2.88 mg/capsule and picroside 2 from 5.50 to 6.00 mg/capsule. In the galactosamine-induced liver injury in rats, Pk at a dose of 200 mg/kg p.o. showed a significant reduction (p < 0.05) in liver lipid content, GOT and GPT. In a randomised, double-blind placebo controlled trial in patients diagnosed to have acute viral hepatitis (HBsAg negative), Pk root powder 375 mg three times a day was given for 2 weeks (n = 15) or a matching placebo (n = 18) was given. Difference in values of bilirubin, SGOT and SGPT was significant between placebo and Pk groups. The time in days required for total serum bilirubin to drop to average value of 2.5 mg% was 75.9 days in placebo as against 27.44 days in Pk group. The present study has shown a biological plausability of efficacy of Pk as supported by clinical trial in viral hepatitis, hepatoprotection in animal model and an approach for standardizing extracts based on picroside content.

    How to cite this article:
    Vaidya AB, Antarkar DS, Doshi JC, Bhatt AD, Ramesh VV, Vora PV, Perissond DD, Baxi AJ, Kale PM. Picrorhiza kurroa (Kutaki) Royle ex Benth as a hepatoprotective agent--experimental & clinical studies. J Postgrad Med 1996;42:105-8

    Complete text found here:;aulast=Vaidya

    Oh and this :

    Picrorhiza kurroa is a well-known herb in the Ayurvedic system of medicine and has traditionally been used to treat disorders of the liver and upper respiratory tract, reduce fevers, and to treat dyspepsia, chronic diarrhea, and scorpion sting. It is a small perennial herb from the Scrophulariaceae family, found in the Himalayan region growing at elevations of 3,000-5,000 meters. Picrorhiza kurroa has a long, creeping rootstock that is bitter in taste, and grows in rock crevices and moist, sandy soil. The leaves of the plant are flat, oval, and sharply serrated. The flowers, which appear June through August, are white or pale purple and borne on a tall spike; manual harvesting of the plant takes place October through December. The active constituents are obtained from the root and rhizomes. The plant is self-regenerating but unregulated over-harvesting has caused it to be threatened to near extinction. Current research on Picrorhiza kurroa has focused on its hepatoprotective, anticholestatic, antioxidant, and immune-modulating activity.[1,2]
    Active Constituents

    Kutkin is the active principal of Picrorhiza kurroa and is comprised of kutkoside and the iridoid glycoside picrosides I, II, and III. Other identified active constituents are apocynin, drosin, and nine cucurbitacin glycosides.[3,4] Apocynin is a catechol that has been shown to inhibit neutrophil oxidative burst in addition to being a powerful anti-inflammatory agent,[5] while the curcubitacins have been shown to be highly cytotoxic and possess antitumor effects.[6]
    Mechanisms of Action
    The hepatoprotective action of Picrorhiza kurroa is not fully understood but may be attributed to Picrorhiza's ability to inhibit the generation of oxygen anions and to scavenge free radicals.[7] Picrorhiza's antioxidant effect has been shown to be similar to that of superoxide dismutase, metal-ion chelators, and xanthine oxidase inhibitors.[8] In rats infected, with malaria, Picrorhiza restored depleted glutathione levels, thereby enhancing detoxification and antioxidation, and helping maintain a normal oxidation-reduction balance.[9] In this same animal model, Picrorhiza also demonstrated an anti-lipid peroxidative effect.[10] Like silymarin, Picrorhiza has been shown to stimulate liver regeneration in rats, possibly via stimulation of nucleic acid and protein synthesis.[11] Picrorhiza's anti-inflammatory action is attributed to the apocynin constituent, which has been shown to have potent anti-inflammatory properties in addition to inhibiting oxidative burst in neutrophils[5] Although the mechanism is unclear, animal studies indicate Picrorhiza's constituents exhibit a strong anticholestatic activity against a variety of liver-toxic substances, appearing to be even more potent than silymarin. Picrorhiza also exhibits a dose-dependent choleretic activity, evidenced by an increase in bile salts and acids, and bile flow.[12]
    Clinical Indications
    Hepatic Insult and Damage
    Numerous animal studies, primarily in rats, have demonstrated that the active constituents of Picrorhiza kurroa are effective at preventing liver toxicity and the subsequent biochemical changes caused by numerous toxic agents. Hepatocytes damaged by exposure to galactosamine, thiocetamide, and carbon tetrachloride were incubated with Picrorhiza constituents. A concentration-dependent restorative effect was observed in regard to normal hepatocyte function.[13] A similar effect was seen when 25 mg/kg/day oral Picrorhiza extract was administered to rats poisoned by aflatoxin B1 exposure. Picrorhiza kurroa significantly prevented the biochemical changes induced by aflatoxin B1.[14] Picrorhiz extract, when given at a dose of 3-12 mg/kg orally for 45 days, was also shown to be effective in reversing ethanol-induced liver damage in rats.[15] In an animal model of hepatic ischemia, rats given Picrorhiza orally at 12 mg/kg daily for 7 days, prior to induced ischemia, demonstrated improved hepatocyte glycogen preservation and reduced apoptosis, compared to control animals.[16] Picrorhiza principals have also shown to be effective in treating Amanita mushroom poisoning in an in vivo animal model.[17] An in vitro study demonstrated Picrorhiza's antioxidant activity by subjecting human Glioma and Hep 3B cells to a hypoxic state. Picrorhiza treatment reduced the cellular damage cause by hypoxia, indicating Picrorhiza constituents may protect against hypoxia/reoxygenation-induced injuries.[18]
    Viral Hepatitis
    Studies indicate Picrorhiza extracts may be of therapeutic value in treating viral hepatitis. An in vitro study investigated anti-hepatitis B-like activity of Picrorhiza and found it to have promising anti-hepatitis B surface antigen activity.[19] In a randomized, double-blind, placebo-controlled trial of 33 patients diagnosed with acute viral hepatitis, 375 mg Picrorhiza root powder was given three times daily for two weeks. The treatment group was comprised of 15 patients; the remaining 18 subjects acted as controls and received placebo. Bilirubin, SGOT, and SGPT values were significantly lower in the treatment group, and the time required for bilirubin values to drop to 2.5 mg% was 27.4 days in the treatment group versus 75.9 days for the placebo group.[20]
    In vivo studies of bronchial obstruction indicate that the drosin constituent of Picrorhiza kurroa prevented allergen- and platelet activating factor-induced bronchial obstruction when given to guinea pigs via inhalant and oral routes. In vitro histamine release was also inhibited by the plant extract.[21] Picrorhiza extract given orally at 25 mg/kg to mice and rats resulted in a concentration-dependent decrease in mast cell degranulation. However, induced bronchospasm was not prevented, indicating a lack of direct post-synaptic histamine receptor blocking activity.[22]
    Dosage and Toxicity
    Picrorhiza is not readily water-soluble and is therefore not usually taken as a tea. While it is ethanol soluble, the bitter taste makes tinctures unpalatable, so it is therefore usually administered as a standardized (4% kutkin) encapsulated powder extract. Typical adult dosage is 400 to 1500 mg/day, with dosages up to 3.5 g/day sometimes being recommended for fevers. Picrorhiza root extracts are widely used in India with no adverse effects having been reported. The [LD.sub.50] of kutkin is greater than 2600 mg/kg in rats with no data available for humans.[23]
    [1.] Atal CK, Sharma ML, Kaul A, Khajuria A. Immunomodulating agents of plant origin. I: preliminary screening. J Ethnopharmacol 1986;18:133-141.
    [2.] Subedi BP. Plant profile: Kutki (Picrorhiza scrophulariifiora). Himalayan Bioresources 2000;4.
    [3.] Weinges K, Kloss P, Henkels WD. Natural products from medicinal plants. XVII. picroside-II, a new 6-vanilloyl-catapol from Picrorhiza kuroa Royle and Benth. Justus Liebigs Ann Chem 1972;759:173-182. [Article in German]
    [4.] Stuppner H, Wagner H. New cucurbitacin glycosides from Picrorhiza kurroa. Planta Med 1989;55:559-563.
    [5.] Simons JM, `t Hart BA, Ip Vai Ching TR, et al. Metabolic activation of natural phenols into selective oxidative burst agonists by activated human neutrophils. Free Radic Biol Med 1990;8:251-258.
    [6.] Stuppner H, Wagner H. New cucurbitacin glycosides from Picrorhiza kurroa. Planta Medica 1989;55:559.
    [7.] Russo A, Izzo AA, Cardile V, et al. Indian medicinal plants as antiradicals and DNA cleavage protectors. Phytomedicine 2001;8:125-132.
    [8.] Chander R, Kapoor NK, Dhawan BN. Picroliv, picroside-I and kutkoside from Picrorhiza kurroa are scavengers of superoxide anions. Biochem Pharmacol 1992;44:180-183.
    [9.] Chander R, Kapoor NK, Dhawan BN. Effect of picroliv on glutathione metabolism in liver and brain of Mastomys natalensis infected with Plasmodium berghei. Indian J Exp Biol 1992;30:711-714.
    [10.] Chander R, Singh K, Visen PK, et al. Picroliv prevents oxidation in serum lipoprotein lipids of Mastomys coucha infected with Plasmodium berghei. Indian J Exp Biol 1998;36:371-374.
    [11.] Singh V, Kapoor NK, Dhawan BN. Effect of picroliv on protein and nucleic acid synthesis. Indian J Exp Biol 1992;30:68-69.
    [12.] Shukla B, Visen PK, Patnaik GK, et al. Choleretic effect of picroliv, the hepatoprotective principle of Picrorhiza kurroa. Planta Med 1991;57:29-33.
    [13.] Visen PK, Saraswat B, Dhawan BN. Curative effect of picroliv on primary cultured rat hepatocytes against different hepatotoxins: an in vitro study. J Pharmacol Toxicol Methods 1998;40:173-179.
    [14.] Rastogi R, Srivastava AK, Rastogi AK. Biochemical changes induced in liver and serum aflatoxin B1-treated male wistar rats: preventive effect of picroliv. Pharmacol Toxicol 2001;88:53-58.
    [15.] Saraswat B, Visen PK, Patnaik GK, Dhawan BN. Ex vivo and in vivo investigations of picroliv from Picrorhiza kurroa in an alcohol intoxication model in rats. J Ethnopharmacol 1999;66:263-269.

    [16.] Singh AK, Mani H, Seth P. Picroliv preconditioning protects the rat liver against ischemia-reperfusion injury. Eur J Pharmacol 2000;395:229-239.
    [17.] Dwivedi Y, Rastogi R, Garg NK, et al. Effects of picroliv, the active principle of Picrorhiza kurroa, on biochemical changes in rat liver poisoned by Amanita phalloides. Chung Kuo Yao Li Hsueh Pao 1992;13:197-200.
    [18.] Gaddipati JP, Madhavan S, Sidhu GS, et al. Picroliv -- a natural product protects cells and regulates the gene expression during hypoxia/reoxygenation. Mol Cell Biochem 1999;194:271-281.
    [19.] Mehrotra R, Rawat S, Kulshreshtha DK, et al. In vitro studies on the effect of certain natural products against hepatitis B virus. Indian J Med Res 1990;92:133-138.
    [20.] Vaidya AB, Antarkar DS, Doshi JC, et al. Picrorhiza kurroa (Kutaki) Royle ex Benth as a hepatoprotective agent -- experimental and clinical studies. J Postgrad Med 1996;42:105-108.
    [21.] Dorsch W, Wagner H. New antiasthmatic drugs from traditional medicine? Int Arch Allergy Appl Immunol 1991;94:262-265.
    [22.] Baruah CC, Gupta PP, Nath A, et al. Anti-allergic and anti-anaphylactic activity of picroliv -- a standardised iridoid glycoside fraction of Picrorhiza kurroa. Pharmacol Res 1998;38:487-492.
    [23.] Annual Report, Regional Research Laboratory, Council for Scientific and Industrial Research, India. 1989-1990.


    Picrorhiza kurroa


    Indian Name :Kutki & Kuru Botanical Name :Picrorhiza kurroa Other Names :Katuka, Kuru & Kadu
    It is a small perennial herb from the Scrophulariaceae family. The rhizome of Picrorhiza has been traditionally used to treat worms, constipation, low fever, scorpion sting, asthma and ailments affecting the liver. Current research on Picrorhiza kurroa has focused on its hepatoprotective, anticholestatic, antioxidant, and immune-modulating activity.
    Picrorhiza kurroa also known as kutki is found in the North-Western Himalayan region from Kashmir to Kumaun and Garhwal regions in India and Nepal.

    Chemical composition / key active constituents
    Kutkin, a bitter glycosidal principle, is reported. Also isolated D-mannitol, vanillic acid and some steroids are present. Kutkin was later shown to be a stable mixed crystal of two C-9 iridoid glycosides-Picroside I and Kutakosid. Apocynin has been isolated from the plant. Picroside II has been isolated and shown to have hepatoprotective activity. With the help of preparative HPLC, larger Quantities of picrosides have been isolated, permitting precise structure identification and biological experiments.

    Alcohloic extract of the plant and kutkin possess hepatoprotective activity. Plant is a potent immunostimulant of both cell mediated and humoral immunity and exhibits choleretic activity in dogs. Picrorhiza kurroa is also benefical in the management of bronchial asthma.
    Remedies For
    Protects the liver against hepatotoxins, hepatoprotective properties, Potent antioxidant activity, Modulates liver enzyme levels, anti-inflammatory action anti-allergy action.

    3-4 gm of drug is generally given as antiperiodic and 0.6-1.2 gm as bitter tonic. Typical adult dosage is 400 to 1500 mg/day, with dosages up to 3.5 g/day sometimes being recommended for fevers
    References:1.Atal CK, Sharma ML, Kaul A, Khajuria A. Immunomodulating agents of plant origin. Ireliminary screening. J Ethnopharmacol 1986;18:133-141. 2.Subedi BP. Plant profile: Kutki (Picrorhiza scrophulariiflora). Himalayan Bioresources 2000;4.3.Weinges K, Kloss P, Henkels WD. Natural products from medicinal plants. XVII.picroside-II, a new 6 -vanilloyl-catapol from Picrorhiza kuroa
    Royle and Benth. Just usLiebigs Ann Chem 1972;759:173-182. [Article in German]4. Stuppner H, Wagner H. New cucurbitacin glycosides from Picrorhiza kurroa. Planta Med 1989; 55:559-563.


    To buy:

    in bulk:

  7. In summation, Picrorhiza Kurroa has a different mechanism of action than Milk Thistle and is possibly a better hepatoprotector, although it is much less available.

    For someone who is ALLERGIC to milk thistle, this is the way to go. I think for anyone who cares about their liver, stacking it with milk thistle is very smart.

  8. Good info, i would add that NAC is certainly another must for liver protection.

  9. Why Milk Thistle hinders results!

    OK, here's some more info on Milk Thistle. I was wondering how one might come to the conclusion that MT might hider results of a cycle. The idea of MT hindering uptake of drugs by the body didn't seem to stick with what was observed at all. It turns out that the pathway through which it hinders results is via an inhibition of the enzymes that convert arachidonic acid to prostaglandins, of which PGF-2a is.

    Now at first this seems to say that those enzymes are super-activated, but it turns out it isn't the case.

    Inhibition of Kupffer cell functions as an explanation for the hepatoprotective properties of silibinin.

    Dehmlow C, Erhard J, de Groot H.

    Institut fur Physiologische Chemie, Universitatsklinikum, Essen, Germany.

    The flavonoid silibinin, the main compound extracted from the milk thistle Silybum marianum, displays hepatoprotective properties in acute and chronic liver injury. To further elucidate the mechanisms by which it acts, we studied the effects of silibinin on different functions of isolated rat Kupffer cells, namely the formation of superoxide anion radical (02-), nitric oxide (NO), tumor necrosis factor alpha (TNF-alpha), prostaglandin E(2) (PGE(2)), and leukotriene B(4) (LTB(4)). Production of 02- and NO were inhibited in a dose-dependent manner, with an 50 percent inhibitory concentration (IC(50)) value around 80 micro mol/L. No effect on TNF-alpha formation was detected. Opposite effects were found on the cyclooxygenase and 5-lipoxygenase pathway of arachidonic acid metabolism. Whereas no influence on PGE(2) formation was observed with silibinin concentrations up to 100 micro mol/L, a strong inhibitory effect on LTB(4) formation became evident. The IC(50)-value for inhibiting the formation of this eicosanoid was determined to be 15 micro mol/L silibinin. The strong inhibition of LTB(4), formation by silibinin was confirmed in experiments with phagocytic cells isolated from human liver. Hence, while rather high concentrations of silibinin are necessary to diminish free radical formation by activated Kupffer cells, significant inhibition of the 5-lipoxygenase pathway already occurs at silibinin concentrations which are achieved in vivo. Selective inhibition of leukotriene formation by Kupffer cells can at least partly account for the hepatoprotective properties of silibinin.

    PMID: 8666328 [PubMed - indexed for MEDLINE]

    In this study I have only highlighted where they say how PGF is dependent upon those enzymes:

    Up-regulation of prostaglandin biosynthesis by leukotriene C4 in elicited mice peritoneal macrophages activated with lipopolysaccharide/interferon-{gamma}.

    Rossi A, Acquaviva AM, Iuliano F, Di Paola R, Cuzzocrea S, Sautebin L.

    Department of Experimental Pharmacology, 'L. Califano', University of Naples Federico II, Naples, Italy.

    Leukotrienes (LT) and prostaglandins (PG) are proinflammatory mediators generated by the conversion of arachidonic acid via 5-lipoxygenase (5-LO) and cyclooxygenase (COX) pathways. It has long been proposed that the inhibition of the 5-LO could enhance the COX pathway leading to an increased PG generation. We have found that in in vitro models of inflammation, such as mice-elicited peritoneal macrophages activated with lipopolysaccharide (LPS)/interferon-gamma (IFN-gamma), the deletion of the gene encoding for 5-LO or the enzyme activity inhibition corresponded to a negative modulation of the COX pathway. Moreover, exogenously added LTC(4), but not LTD(4), LTE(4), and LTB(4), was able to increase PG production in stimulated cells from 5-LO wild-type and knockout mice. LTC(4) was not able to induce COX-2 expression by itself but rather potentiated the action of LPS/IFN-gamma through the extracellular signal-regulated kinase-1/2 activation, as demonstrated by the use of a specific mitogen-activated protein kinase (MAPK) kinase inhibitor. The LT-induced increase in PG generation, as well as MAPK activation, was dependent by a specific ligand-receptor interaction, as demonstrated by the use of a cys-LT1 receptor antagonist, although also a direct action of the antagonist used, on PG generation, cannot be excluded. Thus, the balance between COX and 5-LO metabolites could be of great importance in controlling macrophage functions and consequently, inflammation and tumor promotion.

    PMID: 16046553 [PubMed - in process]

    And here too:

    Pharmacological intervention of cyclooxygenase-2 and 5-lipoxygenase pathways. Impact on inflammation and cancer.

    Claria J, Romano M.

    DNA Unit, Hospital Clinic, and Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, Spain. [email protected]

    Eicosanoids are potent biologically active arachidonic acid-derived lipid mediators that are intimately involved in inflammation and cancer. Cyclooxygenase (COX), the key enzyme in prostaglandin (PG) biosynthesis, controls one of the major pathways of arachidonic acid metabolism and is the main target for non-steroidal anti-inflammatory drugs (NSAIDs). COX exists in two distinct isoforms, COX-1 and COX-2, the latter being primarily involved in inflammation and cell proliferation. For this reason, in recent years, selective COX-2 inhibitors, that achieve the same anti-inflammatory efficacy as traditional NSAIDs but minimize the risk of unwanted side-effects, have been developed. On the other hand, emerging information has appreciated the role of other arachidonic acid metabolic pathway (the 5-lipoxygenase (5-LO) pathway) in producing and maintaining inflammation. Moreover, it is now being perceived that COX-2 and 5-LO have converging functions not only in inflammation but also in cell proliferation and neo-angiogenesis. In this regard, there is evidence that COX-2 and 5-LO are co-expressed and up-regulated in a number of inflammatory and neoplastic disorders, and that COX-2 as well as 5-LO inhibitors have beneficial effects in inflammatory diseases and are being investigated as potential anticancer drugs. This review provides an overview and an update of the progress achieved in the knowledge of COX-2 and 5-LO pathways and their involvement in inflammation and cancer. It also proposes a model of integrated pharmacological intervention on these pathways and reviews the information available regarding the use of the novel dual COX-2/5-LO inhibitors that block both pathways equally well.

    PMID: 16250846 [PubMed - in process]

    Well, so, that's that. NAC, k-r-ALA...

    About Picrorhiza kurroa

    Cyclooxygenase-2 enzyme inhibitory triterpenoids from Picrorhiza kurroa seeds.

    Zhang Y, Dewitt DL, Murugesan S, Nair MG.

    Bioactive Natural Products and Phytoceuticals, Department of Horticulture and National Food Safety and Toxicology Center, Michigan State University, East Lansing, Michigan 48824, USA.

    A bioassay guided phytochemical study of the ethyl acetate extract of the seeds of Picrorhiza kurroa afforded a new triterpenoid, 2alpha, 3beta, 19beta, 23-tetrahydroxyolean-12-en-28-O-beta-D-glucoside (1), along with five known triterpenoids, 2alpha, 3beta, 19beta, 23-tetrahydroxyolean-12-en-28-oic acid (2), 2alpha, 3beta, 23-trihydroxyolean-12-en-28-O-beta-d-glucoside (3), 2alpha, 3beta, 23-trihydroxyolean-12-en-28-oic acid (4), 2alpha, 3beta, 19beta, trihydroxyolean-12-en-28-oic acid (5), and 2alpha, 3beta, 6beta, 23-tetrahydroxyolean-12-en-28-oic acid (6). Their structures were established by extensive NMR spectral studies. The acetyl derivatives, compounds 7 and 8, were prepared from compounds 1 and 2, respectively, to aid in their structure elucidation. The inhibition of cyclooxygenase-2 (COX-2) enzyme by compounds 1--6 at 100 microg/mL was 38.3%, 39%, 37%, 49.6%, 25%, and 45.0%, respectively. However, compounds 1--6, at 100 microg/mL, did not inhibit cyclooxygenase-1 (COX-1) enzyme. Compound 1 is a novel triterpenoid and compounds 1--6 are isolated for the first time from the seeds of P. kurroa.

    PMID: 15979098 [PubMed - indexed for MEDLINE]

    Now, of course, I don't know if COX-1 or COX-2 is more important for the synthesis of PGF2a and the resulting anabolism. Will search. EDIT : This says that COX-2 is much more important in inflammation mechanisms than COX-1. What this means for muscle growth I do not know. Maybe someone can help? Here's the excerpt:

    Distribution of cyclooxygenase isoforms in murine chronic granulomatous inflammation. Implications for future anti-inflammatory therapy.

    Appleton I, Tomlinson A, Mitchell JA, Willoughby DA.

    Department of Experimental Pathology, William Harvey Research Institute, St. Bartholomew's Hospital Medical College, London, U.K.

    Inhibition of the enzyme cyclooxygenase (COX) is the basis for the mechanism of action of non-steroidal anti-inflammatory drugs (NSAIDs). COX exists as a constitutive (COX-1) and a mitogen-inducible (COX-2) isoform. The relative contribution of COX-1 and COX-2 to inflammation is unknown. This study investigated COX activity and the distribution of COX-1 and COX-2 during the development of a murine air pouch model of chronic granulomatous inflammation. COX activity progressively rose and was maximal at day 14. Of the COX metabolites measured, PGE2 was the greatest > 6-keto PGF1a > TXB2 > PGF2a. By day 7, COX-2-labelled fibroblast- and macrophage-like cells were observed and their number and distribution increased with time. At all time points, endothelial cells of venules in the loose connective tissue of the dermis showed immunoreactivity for COX-2. After day 14, labelling of capillaries in the granuloma was also observed. This study is the first to show that COX-2 is the predominant COX isoform in all stages of the inflammatory response. These results suggest that selective inhibition of COX-2 may prove more beneficial, with fewer gastric and renal side-effects, than existing NSAID therapy for the treatment of chronic inflammatory diseases.

    PMID: 7562257 [PubMed - indexed for MEDLINE]

    Stopping here, although it would be nice to know if all we need to look for is either COX-1 or COX-2 inhibition from whatever we take...

  10. @grunt, VERY interesting, thanks ! how can I give you rep points ? And here's something I found about the metabolism of AA acid, it seems that both COX1 and 2 are involved in the production of the PGH family of prostaglandins,
    Attached Images Attached Images   

  11. Click on the little scale in this or the previous post of MINE then click on "I approve" and then you can enter a comment like "You da man". You can see the points you receive or lose in the user CP, which also lists your subscribed threads. Pretty nifty board, this is.

    Seriously, thanks for these 2 images, they complete the above research splendidly!

  12. ok grunt just did it, so concerning milk thistle I think it should be used PCT, for example I'm gonna just use LIV 52 throughout my 20 weeker at 3 caps ED, although I'll use drol only for 3 weeks I think liv 52 is the most complete formula

  13. Thanks for the reps!

    And yeah man, sounds right. I'mma preload MT like good for a few weeks, then switch over to good ole NAC and perhaps curcumin, then back to MT during PCT or maybe AFTER pct and keeping the NAC. This seems to be another reason to keep the orals cycles short! I'm going to work on an optimized liver-protection protocol based on these findings.

    And I'm gonna do 4-weekers myself from now on.

    Life has got to be good when you live at a place that's called "Free Juice"? Joking man, my mother tongue is French.

  14. lol bro, juice isn't free in france, you mean by that it's legal ? If so, hell no it's not legal, plus it's hard to find good sources, I know a guy who bought enanthate amps at 10 euros (15 dollars) for one ! Either people here are ignorant (99% of them are) or they are scammers. I never buy my **** locally.

  15. Wait, people actually gave you negative rep because they weren't spoon fed the details and couldnt read for themselves? I thought this board was big on research and learning. I'm giving you positive rep just for spite!

  16. After full consideration of this research and the very limited stuff I found about NAC, here is my liver protection plan for my next few cycles.

    Pre-cycle, milk thistle preload @ double dose
    ON cycle, NAC & standard dose milk thistle
    PCT, high-dose NAC only

    Why? Because during PCT the androgens are mostly gone so liver protection isn't paramount at that time, plus the LAST thing you need in PCT is something that might hinder results.

    Well that's my rationale for it and as always I'm looking for other angles if there are any...


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