Roy S. Kaur M. Agarwal C. Tecklenburg M. Sclafani RA. Agarwal R. p21 and p27 induction by silibinin is essential for its cell cycle arrest effect in prostate carcinoma cells. Molecular Cancer Therapeutics. 6(10):2696-707, 2007 Recent studies have shown that silibinin induces p21/Cip1 and p27/Kip1 and G1 arrest in different prostate cancer cells irrespective of p53 status; however, biological significance and mechanism of such induction have not been studied. Here, using two different prostate cancer cell lines DU145 and 22Rv1, representing androgen-independent and androgen-dependent stages of malignancy, first we investigated the importance of p21 and p27 induction in silibinin-mediated G1 arrest. Silencing p21 and p27 individually by RNA interference showed marked reversal in G1 arrest; however, their simultaneous ablation showed additional reversal of G1 arrest in 22Rv1 but not DU145 cells. These results suggest that whereas relative importance of these molecules might be cell line specific, their induction by silibinin is essential for its G1 arrest effect. Next, studies were done to examine mechanisms of their induction where cycloheximide-chase experiments showed that silibinin increases p21 and p27 protein half-life. This effect was accompanied by strong reduction in Skp2 level and its binding with p21 and p27 together with strong decrease in phosphorylated Thr(187) p27 without considerable change in proteasomal activity, suggesting a posttranslational mechanism. Skp2 role was further elucidated using Skp2-small interfering RNA-transfected cells, where decreased G1 arrest and attenuated Cip/Kip induction were observed with silibinin treatment. Further, silibinin caused a marked increase in p21 and p27 mRNA levels together with an increase in their promoter activity, also indicating a transcriptional mechanism. Together, our results for the first time identify a central role of p21 and p27 induction and their regulatory mechanism in silibinin-mediated cell cycle arrest.
Song Z. Song M. Lee DY. Liu Y. Deaciuc IV. McClain CJ. Silymarin prevents palmitate-induced lipotoxicity in HepG2 cells: involvement of maintenance of Akt kinase activation. Basic & Clinical Pharmacology & Toxicology. 101(4):262-8, 2007 Whereas adipocytes have a unique capacity to store excess free fatty acids in the form of triglyceride in lipid droplets, non-adipose tissues, such as liver, have a limited capacity for storage of lipids. Saturated long-chain fatty acids, such as palmitate, are the major contributors to lipotoxicity. Silymarin is a mixture of flavonolignans, extracted from the milk thistle (Silibum marianum). Its hepatoprotective properties have been studied both in vitro and in vivo; however, its effect on palmitate-induced lipotoxicity has not been investigated. The objective of this study was to investigate (i) whether silymarin could protect HepG2 cells from palmitate-induced cell death in an in vitro model, and (ii) possible mechanisms involved in this hepatoprotective role of silymarin. HepG2 cells were treated with palmitate in the absence or presence of silymarin and supernatants or cell lysates were collected at varying time-points. Cell death was assayed by measuring DNA fragmentation, caspase-3 activity and lactate dehydrogenase release. Lipid peroxidation was assessed by measuring malondialdehyde and 4-hydroxyalkenals. Akt kinase activity was also measured. Incubation with palmitate caused significant death in HepG2 cells. Palmitate incubation did not cause significant changes in reactive oxygen species production or intracellular glutathione content, but markedly inhibited Akt kinase activity. Pre-treatment of HepG2 cells with silymarin prevented palmitate-induced inhibition of Akt kinase activity and attenuated cell death. Our results suggest that silymarin may be an effective agent in protecting hepatocytes from saturated fatty acids-induced cell death. These data also provide a further rationale for exploration of the use of silymarin in the treatment of non-alcoholic steatohepatitis.
Svobodova A. Zdarilova A. Walterova D. Vostalova J. Flavonolignans from Silybum marianum moderate UVA-induced oxidative damage to HaCaT keratinocytes. Journal of Dermatological Science. 48(3):213-24, 2007 BACKGROUND: UV radiation from sunlight is a very potent environmental risk factor in the pathogenesis of skin cancer. Exposure to UV light, especially the UVA part, provokes the generation of reactive oxygen species (ROS), which induce oxidative stress in exposed cells. Topical application of antioxidants is a successful strategy for protecting the skin against UV-caused oxidative damage. OBJECTIVE: In this study, silybin (SB) and 2,3-dehydrosilybin (DS) (1-50 micromol/l), flavonolignan components of Silybum marianum, were tested for their ability to moderate UVA-induced damage. METHODS: Human keratinocytes HaCaT were used as an appropriate experimental in vitro model, to monitor the effects of SB and DS on cell viability, proliferation, intracellular ATP and GSH level, ROS generation, membrane lipid peroxidation, caspase-3 activation and DNA damage. RESULTS: Application of the flavonolignans (1-50 micromol/l) led to an increase in cell viability of irradiated (20 J/cm(2)) HaCaT keratinocytes. SB and DS also suppressed intracellular ATP and GSH depletion, ROS production and peroxidation of membrane lipids. UVA-induced caspases-3 activity/activation was suppressed by treatment with SB and DS. Lower concentrations of both compounds (10 micromol/l) significantly reduced cellular DNA single strand break formation. CONCLUSION: Taken together, the results suggest that these flavonolignans suppress UVA-caused oxidative stress and may be useful in the treatment of UVA-induced skin damage.
MacKinnon SL. Hodder M. Craft C. Simmons-Boyce J. Silyamandin, a new flavonolignan isolated from milk thistle tinctures. Planta Medica. 73(11):1214-6, 2007 Our investigations into the stability of tincture preparations of milk thistle fruit [ Silybum marianum L. Gaertn. (Asteraceae)] have led to the characterization of a new flavonolignan 4-(4-hydroxy-3-methoxyphenyl)-7-[(2 R,3 R)-3,5,7-trihydroxy-4-oxochroman-2-yl]-1-oxo-1,3,3a,4,5,7a-hexahydro-2-benzofuran-5-carboxylic acid called silyamandin (1). Incubation of the tincture at 40 degrees C for 3 months resulted in an increase in the level of this compound, as observed in the LC/DAD silymarin profile.
White CP. Hirsch G. Patel S. Adams F. Peltekian KM. Complementary and alternative medicine use by patients chronically infected with hepatitis C virus. Canadian Journal of Gastroenterology. 21(9):589-95, 2007 Complementary and alternative medicine (CAM) is becoming increasingly popular in North America. The use of CAM is also popular in patients with chronic liver disease but is not well documented. The extent of use of CAM in chronic hepatitis C virus (HCV) infected patients was determined, and the demographic and clinical data between users and nonusers of CAM was compared. Seventy-six patients (30% female) with chronic HCV were interviewed. The mean age was 43+/-8 years. Current use of CAM for HCV was reported by 35 of 76 patients (46%). Eighteen of 76 patients within this group used herbal supplements (24%). The most commonly used herb was Silybum marianum (milk thistle), reported by 10 of 76 patients (13.2%). Commonly reported benefits of CAM use included reduction in fatigue, boost in the immune system and improved gastrointestinal function. No adverse effects of CAM use were reported. In the present study, four of 18 patients (22%) with chronic liver disease taking herbal therapies were on herbs that increased bleeding time. The use of CAM in chronic HCV patients is significant. Patients should be asked specifically about their use of CAM. CAM use may have implications affecting conventional treatment and management of HCV.
Etheridge AS. Black SR. Patel PR. So J. Mathews JM. An in vitro evaluation of cytochrome P450 inhibition and P-glycoprotein interaction with goldenseal, Ginkgo biloba, grape seed, milk thistle, and ginseng extracts and their constituents. Planta Medica. 73(8):731-41, 2007 Drug-herb interactions can result from the modulation of the activities of cytochrome P450 (P450) and/or drug transporters. The effect of extracts and individual constituents of goldenseal, Ginkgo biloba (and its hydrolyzate), grape seed, milk thistle, and ginseng on the activities of cytochrome P450 enzymes CYP1A2, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4 in human liver microsomes were determined using enzyme-selective probe substrates, and their effect on human P-glycoprotein (Pgp) was determined using a baculovirus expression system by measuring the verapamil-stimulated, vanadate-sensitive ATPase activity. Extracts were analyzed by HPLC to standardize their concentration(s) of constituents associated with the pharmacological activity, and to allow comparison of their effects on P450 and Pgp with literature values. Many of the extracts/constituents exerted > or = 50 % inhibition of P450 activity. These include those from goldenseal (normalized to alkaloid content) inhibiting CYP2C8, CYP2D6, and CYP3A4 at 20 microM, ginkgo inhibiting CYP2C8 at 10 microM, grape seed inhibiting CYP2C9 and CYP3A4 at 10 microM, milk thistle inhibiting CYP2C8 at 10 microM, and ginsenosides F1 and Rh1 (but not ginseng extract) inhibiting CYP3A4 at 10 microM. Goldenseal extracts/constituents (20 microM, particularly hydrastine) and ginsenoside Rh1 stimulated ATPase at about half of the activity of the model substrate, verapamil (20 microM). The data suggest that the clearance of a variety of drugs may be diminished by concomitant use of these herbs via inhibition of P450 enzymes, but less so by Pgp-mediated effects.
Sagar SM. Future directions for research on Silybum marianum for cancer patients. [Review] [40 refs] Integrative Cancer Therapies. 6(2):166-73, 2007 J Silymarin (Silybum marianum [L.] Gaertn. [Asteraceae]) is a promising agent for cancer prevention, adjuvant cancer treatment, and reduction of iatrogenic toxicity. Although it is safe and free of serious adverse side effects, few studies have evaluated its use alongside conventional cytotoxic therapies, and adverse events associated with long-term administration are uncertain. Although it may prevent some types of cancer, its promotion of tissue regeneration and its potential estrogen activity could promote the growth of some tumors. Further clinical trials using authenticated fractions of silymarin as simple and complex derivatives are required prior to any general recommendations. Future research should focus on authentication of active chemicals, pharmacokinetics, adverse interactions and quality control, prevention of cancer initiation and progression, adjuvant therapy for specific cancers, and prevention of toxicity from anticancer therapies.
Greenlee H. Abascal K. Yarnell E. Ladas E. Clinical applications of Silybum marianum in oncology.[see comment]. [Review] [75 refs] Integrative Cancer Therapies. 6(2):158-65, 2007 Milk thistle (Silybum marianum) is an herb that is increasingly used in oncology research and treatment settings. Historically, it has been used to treat liver and biliary disorders and has been used in detoxification and cleansing protocols. However, milk thistle is increasingly being investigated for its use in adult and pediatric populations for oncology indications. Possible indications during cancer treatment include cleansing and detoxification after chemotherapy, preventing hepatotoxicity during chemotherapy, treating hepatotoxicity after chemotherapy, and potentiating chemotherapy and radiation therapy as an adjunctive treatment. Milk thistle may also have applications in ameliorating long-term hepatic and cardiovascular effects of cancer treatment. Preliminary studies are investigating its use as a chemopreventive agent and possibly to treat cancer directly. Much of milk thistle's current clinical use grows out of historical uses but is informed by an increasing number of clinical trials and animal studies. This article provides an overview of the current clinical applications of milk thistle in the oncology setting, including guidelines on commonly used forms and doses.
Tamayo C. Diamond S. Review of clinical trials evaluating safety and efficacy of milk thistle (Silybum marianum [L.] Gaertn.). [Review] [64 refs] Integrative Cancer Therapies. 6(2):146-57, 2007 Milk thistle extracts have been used as traditional herbal remedies for almost 2000 years. The extracts are still widely used to protect the liver against toxins and to control chronic liver diseases. Recent experimental and clinical studies suggest that milk thistle extracts also have anticancer, antidiabetic, and cardioprotective effects. This article reviews clinical trials of milk thistle conducted in the past 5 years including pharmacokinetic and toxicity studies, herb-drug interactions, and other safety issues. Several trials have studied the effects of milk thistle for patients with liver diseases, cancer, hepatitis C, HIV, diabetes, and hypercholesterolemia. Promising results have been reported in the protective effect of milk thistle in certain types of cancer, and ongoing trials will provide more evidence about this effect. In addition, new established doses and improvement on the quality and standardization of this herb will provide the much-awaited evidence about the efficacy of milk thistle in the treatment of liver diseases. Milk thistle extracts are known to be safe and well tolerated, and toxic or adverse effects observed in the reviewed clinical trials seem to be minimal. The future of milk thistle research is promising, and high-quality randomized clinical trials on milk thistle versus placebo may be needed to further demonstrate the safety and efficacy of this herb.
Post-White J. Ladas EJ. Kelly KM. Advances in the use of milk thistle (Silybum marianum).[comment]. [Review] [60 refs] Integrative Cancer Therapies. 6(2):104-9, 2007 Milk thistle (Silybum marianum) is an herbal supplement used to treat liver and biliary disorders. Silymarin, a mixture of flavanoid complexes, is the active component that protects liver and kidney cells from toxic effects of drugs, including chemotherapy. Although milk thistle has not significantly altered the course of chronic liver disease, it has reduced liver enzyme levels and demonstrated anti-inflammatory and T cell-modulating effects. There is strong preclinical evidence for silymarin's hepatoprotective and anticarcinogenic effects, including inhibition of cancer cell growth in human prostate, skin, breast, and cervical cells. Milk thistle is considered safe and well-tolerated, with gastrointestinal upset, a mild laxative effect, and rare allergic reaction being the only adverse events reported when taken within the recommended dose range. More clinical trials of rigorous methodology, using standardized and well-defined products and dosages, are needed to evaluate the potential of silymarin against liver toxicity, chronic liver disease, and human cancers.
Rotem C. Kaplan B. Phyto-Female Complex for the relief of hot flushes, night sweats and quality of sleep: randomized, controlled, double-blind pilot study. Gynecological Endocrinology. 23(2):117-22, 2007 OBJECTIVE: To determine the efficacy and safety of the herbal formula Phyto-Female Complex (SupHerb, Netanya, Israel; ingredients: standardized extracts of black cohosh, dong quai, milk thistle, red clover, American ginseng, chaste-tree berry) for the relief of menopausal symptoms. METHODS: A randomized, double-blind, placebo-controlled trial in 50 healthy pre and postmenopausal women, aged 44-65 years, to whom oral Phyto-Female Complex or matched placebo was prescribed twice daily for 3 months. A structured questionnaire on the frequency and intensity of menopausal symptoms was administered weekly from one week before throughout the 3-month treatment period, followed by biochemical tests, breast check, and transvaginal ultrasonography. RESULTS: The women receiving Phyto-Female Complex reported a significantly superior mean reduction in menopausal symptoms than the placebo group. The effect of treatment improvements in menopausal symptoms increased over time; by 3 months there was a 73% decrease in hot flushes and a 69% reduction of night sweats, accompanied by a decrease in their intensity and a significant benefit in terms of sleep quality. Hot flushes ceased completely in 47% of women in the study group compared with only 19% in the placebo group. There were no changes in findings on vaginal ultrasonography or levels of relevant hormones (estradiol, follicle-stimulating hormone), liver enzymes or thyroid-stimulating hormone in either group. CONCLUSION: Phyto-Female Complex is safe and effective for the relief of hot flushes and sleep disturbances in pre- and postmenopausal women, at least for 3 months' use.
Nencini C. Giorgi G. Micheli L. Protective effect of silymarin on oxidative stress in rat brain. Phytomedicine. 14(2-3):129-35, 2007 Brain is susceptible to oxidative stress and it is associated with age-related brain dysfunction. Previously, we have pointed out a dramatic decrease of glutathione levels in the rat brain after acetaminophen (APAP) oral administration overdose. Silymarin (SM) is a mixture of bioactive flavonolignans isolated from Silybum marianum (L.) Gaertn., employed usually in the treatment of alcoholic liver disease and as anti-hepatotoxic agent in humans. In this study, we have evaluated the effect of SM on enzymatic and non enzymatic antioxidant defensive systems in rat brain after APAP-induced damage. Male albino Wistar rats were treated with SM (200 mg/kg/die orally) for three days, or with APAP single oral administration (3 g/kg) or with SM (200 mg/kg/die orally) for 3 days and APAP single oral administration (3 g/kg) at third day. Successively the following parameters were measured: reduced and oxidized glutathione (GSH and GSSG), ascorbic acid (AA), enzymatic activity variations of superoxide dismutase (SOD) and malondialdehyde levels (MDA). Our results showed a significant decrease of GSH levels, AA levels and SOD activity and an increase of MDA and GSSG levels after APAP administration. After SM administration GSH and AA significantly increase and SOD activity was significantly enhanced. In the SM+APAP group, GSH values significantly increase and the others parameters remained unchanged respect to control values. These results suggest that SM may to protect the SNC by oxidative damage for its ability to prevent lipid peroxidation and replenishing the GSH levels.
Chen PN. Hsieh YS. Chiou HL. Chu SC. Silibinin inhibits cell invasion through inactivation of both PI3K-Akt and MAPK signaling pathways. Chemico-Biological Interactions. 156(2-3):141-50, 2005 Silibinin, isolated from Silybum marianum, has been known for its hepatoprotective properties and recent studies have revealed its antiproliferative and apoptotic effects on several cancer cells. An inhibitory effect of silibinin on tumor invasion and matrix metalloproteinase-2 (MMP-2) and urokinasetype plasminogen activator (u-PA) activities in culture medium has been observed in our previous study and the impacts of silibinin on enzyme activities of MMPs, u-PA, mitogen-activated protein kinase (MAPK) and Akt in A549 cells were continued to explore in this study. Our results showed that silibinin exerted an inhibitory effect on the phosphorylation of Akt, as well as extracellular signal-regulated kinases 1 and 2 (ERK1/2), which are the members of the MAPK family involved in the up-regulation of MMPs or u-PA, while no effects on the activities of p38(MAPK) and stress-activated protein kinase/c-Jun N-terminal kinase were observed. A treatment with silibinin to A549 cells also led to a dose-dependent inhibition on the activation of NF-kappaB, c-Jun and c-Fos. Additionally, the treatment of inhibitors specific for MEK (U0126) or PI3K (LY294002) to A549 cells could result in a reduced expression of MMP-2 and u-PA concomitantly with a marked inhibition on cell invasion. These findings suggested that the inhibition on MMP-2 and u-PA expression by silibinin may be through a suppression on ERK1/2 or Akt phosphorylation, which in turn led to the reduced invasiness of the cancer cells.
Rambaldi A. Jacobs BP. Gluud C. Milk thistle for alcoholic and/or hepatitis B or C virus liver diseases.[update of Cochrane Database Syst Rev. 2005;(2):CD003620; PMID: 15846671]. [Review] [145 refs] Cochrane Database of Systematic Reviews. (4):CD003620, 2007. BACKGROUND: Alcohol and hepatotoxic viruses cause the majority of liver diseases. Randomised clinical trials have assessed whether extracts of milk thistle, Silybum marianum (L) Gaertneri, have any effect in patients with alcoholic and/or hepatitis B or C virus liver diseases. OBJECTIVES: To assess the beneficial and harmful effects of milk thistle or milk thistle constituents versus placebo or no intervention in patients with alcoholic liver disease and/or viral liver diseases (hepatitis B and hepatitis C). SEARCH STRATEGY: The Cochrane Hepato-Biliary Group Controlled Trials Register, The Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, and full text searches were combined (July 2007). Manufacturers and researchers in the field were contacted. SELECTION CRITERIA: Only randomised clinical trials in patients with alcoholic and/or hepatitis B or C virus liver diseases (acute and chronic) were included. Interventions encompassed milk thistle at any dose or duration versus placebo or no intervention. The trials could be double blind, single blind, or unblinded. The trials could be unpublished or published and no language limitations were applied. DATA COLLECTION AND ANALYSIS: The primary outcome measure was mortality. Binary outcomes are reported as relative risks (RR) with 95% confidence interval (CI). Subgroup analyses were performed with regard to methodological quality. MAIN RESULTS: Eighteen randomised clinical trials assessed milk thistle in 1088 patients with alcoholic and/or hepatitis B or C virus liver diseases. The methodological quality was low: only 28.6% of the trials reported high methodological quality characteristics. Milk thistle versus placebo or no intervention had no significant effect on mortality (RR 0.78, 95% CI 0.53 to 1.15), complications of liver disease (RR 0.95, 95% CI 0.83 to 1.09), or liver histology. Liver-related mortality was significantly reduced by milk thistle in all trials (RR 0.50, 95% CI 0.29 to 0.88), but not in high-quality trials (RR 0.57, 95% CI 0.28 to 1.19). Milk thistle was not associated with a significantly increased risk of adverse events (RR 0.83, 95% CI 0.46 to 1.50). AUTHORS' CONCLUSIONS: Our results question the beneficial effects of milk thistle for patients with alcoholic and/or hepatitis B or C virus liver diseases and highlight the lack of high-quality evidence to support this intervention. Adequately conducted and reported randomised clinical trials on milk thistle versus placebo are needed.
Strickland GT. Tanamly MD. Tadros F. Labeeb S. Makld H. Nessim D. Mikhail N. Magder LS. Afdhal NH. Medhat A. Abdel-Hamid M. Two-year results of a randomised double-blinded trial evaluating silymarin for chronic hepatitis C. Digestive & Liver Disease. 37(7):542-3, 2005 Our results question the beneficial effects of milk thistle for patients with alcoholic and/or hepatitis B or C virus liver diseases and highlight the lack of high-quality evidence to support this intervention. Adequately conducted and reported randomised clinical trials on milk thistle versus placebo are needed.
Ball KR. Kowdley KV. A review of Silybum marianum (milk thistle) as a treatment for alcoholic liver disease. [Review] [85 refs] Journal of Clinical Gastroenterology. 39(6):520-8, 2005 Silybum marianum (milk thistle) and its derivatives have been used for centuries for the treatment of liver disease. This review focuses exclusively on published literature pertaining to the potential use of Silybum marianum or its derivatives for the treatment of alcoholic liver disease. Clinical studies have varied greatly in quality, with the majority limited by inadequate sample size, lack of uniformity in the population treated, lack of standardization of preparations studied, variability in dosing regimens, inconsistent outcome measures, and lack of information on concurrent use of alcohol during the treatment period. While Silybum marianum and its derivatives appear to be safe and the available evidence on the mechanisms of action appears promising, there are currently insufficient data from well-conducted clinical trials to recommend their use in patients with alcoholic liver disease.
Mills E. Wilson K. Clarke M. Foster B. Walker S. Rachlis B. DeGroot N. Montori VM. Gold W. Phillips E. Myers S. Gallicano K. Milk thistle and indinavir: a randomized controlled pharmacokinetics study and meta-analysis. European Journal of Clinical Pharmacology. 61(1):1-7, 2005
Lieber CS. Leo MA. Cao Q. Ren C. DeCarli LM. Silymarin retards the progression of alcohol-induced hepatic fibrosis in baboons. Journal of Clinical Gastroenterology. 37(4):336-9, 2003 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.
Ladas EJ. Kelly KM. Milk thistle: is there a role for its use as an adjunct therapy in patients with cancer?. [Review] [43 refs] Journal of Alternative & Complementary Medicine. 9(3):411-6, 2003 The use of complementary and alternative medicine (CAM) is common among patients with cancer. Many of these patients use CAM therapies to decrease the risk of late effects that are sometimes associated with cancer therapy. Certain classes of effective anticancer agents can induce short- and long-term toxicity to the liver. Currently, there are no safer alternatives to these medications. Milk thistle (Silybum marianum) is a botanical that may be useful in the prevention or treatment of liver dysfunction in patients undergoing anticancer therapy.
Jacobs BP. Dennehy C. Ramirez G. Sapp J. Lawrence VA. Milk thistle for the treatment of liver disease: a systematic review and meta-analysis. [Review] [84 refs] American Journal of Medicine. 113(6):506-15, 2002 PURPOSE: Milk thistle, an herbal compound, is the dietary supplement taken most frequently by patients with chronic liver disease. We performed a systematic review of the literature to determine the efficacy and safety of this herb for the treatment of liver disease. METHODS: We searched English and non-English reports through July 1999 using thirteen databases and reference lists, and contacting manufacturers and technical experts. Reviewers independently screened all reports to identify randomized placebo-controlled trials that evaluated milk thistle for the treatment of liver disease. Outcomes of primary interest included mortality, histological findings on liver biopsy specimens, serum aminotransferase and albumin levels, and prothrombin times. RESULTS: Fourteen trials met inclusion criteria. Four trials reported outcomes for mortality among 433 participants. The overall summary odds ratio for mortality in the milk thistle group compared with placebo was 0.8 (95% confidence interval [CI]: 0.5 to 1.5; P = 0.6). Three trials assessed histology on liver biopsy; study quality was inversely associated with the likelihood of histological benefit for milk thistle compared with placebo. There were no differences in serum alanine aminotransferase, aspartate aminotransferase, or albumin levels, or prothrombin times, among participants assigned to milk thistle compared with those assigned to placebo. The only statistically significant difference was a greater reduction in alanine aminotransferase levels among patients with chronic liver disease assigned to milk thistle (-9 IU/L, 95% CI: -18 to -1 IU/L; P = 0.05), but this reduction was of negligible clinical importance and no longer statistically significant after limiting analyses to studies of longer duration or of higher quality. The frequency of adverse effects was low and, in clinical trials, indistinguishable from placebo. CONCLUSION: Treatment with milk thistle appears to be safe and well tolerated. We found no reduction in mortality, in improvements in histology at liver biopsy, or in biochemical markers of liver function among patients with chronic liver disease. Data are too limited to exclude a substantial benefit or harm of milk thistle on mortality, and also to support recommending this herbal compound for the treatment of liver disease.
Bean P. The use of alternative medicine in the treatment of hepatitis C. [Review] [14 refs] American Clinical Laboratory. 21(4):19-21, 2002 More than one-third of Americans use herbs for health purposes, yet patients and physicians usually lack accurate information about safety and efficacy of herbal remedies. In recent years, there has been a substantial increase in the use of so-called complementary and alternative therapies by patients with liver disease. Medical professionals and laboratorians need to be informed about popular alternative therapies and be open-minded to the possibility that some benefit may come from some therapies currently regarded as alternative. Silymarin extracted from the milk thistle is most widely subscribed to as a remedy for liver diseases. The beneficial effects of silymarin are most often seen in the patients who had cirrhosis as a result of alcohol abuse. An ongoing clinical trial will provide some insight as to whether milk thistle directly affects HCV. Silymarin has a good safety record and only rare case reports of gastrointestinal disturbances and allergic skin rashes have been published. The active component of licorice root, glycyrrhizin, has been shown to reduce alanine transaminase and aspartate transaminase values in the serum. This protective function has recently been explained as the inhibitory effects of glycyrrhizin on immune-mediated cytotoxicity against hepatocytes and on nuclear factor (NF)-kappa B, which activates genes encoding inflammatory cytokines in the liver. Finally, some patients with hepatitis C take St. John's Wort and ginger to treat the side effects caused by interferon therapy. An excellent review of this subject was recently published by the NCCAM.
