Milk Thistle: The plant Silybum marianum in the family ASTERACEAE containing the bioflavonoid complex SILYMARIN. For centuries this has been used traditionally to treat liver disease. Silybum marianum (L.) Gaertn. = Carduus marianus L.Silymarin: A mixture of flavonoids extracted from seeds of the MILK THISTLE, Silybum marianum. It consists primarily of silybin and its isomers, silicristin and silidianin. Silymarin displays antioxidant and membrane stabilizing activity. It protects various tissues and organs against chemical injury, and shows potential as an antihepatoxic agent.Flavonolignans: Heterodimers of FLAVONOIDS bound to LIGNANS.Antioxidants: Naturally occurring or synthetic substances that inhibit or retard the oxidation of a substance to which it is added. They counteract the harmful and damaging effects of oxidation in animal tissues.Cimicifuga: A plant genus of the family RANUNCULACEAE that contains triterpenoid saponins. Remifemin from C. racemosa is used to suppress LUTEINIZING HORMONE. It is reclassified by some to ACTAEA. The common name of black snakeroot is also used with ASARUM and SANICULA.Hydrastis: A plant genus of the family RANUNCULACEAE. Members contain BERBERINE.Carduus: A plant genus of the family ASTERACEAE. Members contain arctiin and onopordopicrin.PennsylvaniaLiver Diseases: Pathological processes of the LIVER.Faculty, Medical: The teaching staff and members of the administrative staff having academic rank in a medical school.Schools, Medical: Educational institutions for individuals specializing in the field of medicine.Hepatitis C, Chronic: INFLAMMATION of the LIVER in humans that is caused by HEPATITIS C VIRUS lasting six months or more. Chronic hepatitis C can lead to LIVER CIRRHOSIS.Egypt: A country in northern Africa, bordering the Mediterranean Sea, between Libya and the Gaza Strip, and the Red Sea north of Sudan, and includes the Asian Sinai Peninsula Its capital is Cairo.Hepatitis C: INFLAMMATION of the LIVER in humans caused by HEPATITIS C VIRUS, a single-stranded RNA virus. Its incubation period is 30-90 days. Hepatitis C is transmitted primarily by contaminated blood parenterally, and is often associated with transfusion and intravenous drug abuse. However, in a significant number of cases, the source of hepatitis C infection is unknown.Hepacivirus: A genus of FLAVIVIRIDAE causing parenterally-transmitted HEPATITIS C which is associated with transfusions and drug abuse. Hepatitis C virus is the type species.Cost-Benefit Analysis: A method of comparing the cost of a program with its expected benefits in dollars (or other currency). The benefit-to-cost ratio is a measure of total return expected per unit of money spent. This analysis generally excludes consideration of factors that are not measured ultimately in economic terms. Cost effectiveness compares alternative ways to achieve a specific set of results.Liver Cirrhosis: Liver disease in which the normal microcirculation, the gross vascular anatomy, and the hepatic architecture have been variably destroyed and altered with fibrous septa surrounding regenerated or regenerating parenchymal nodules.Liver Diseases, Alcoholic: Liver diseases associated with ALCOHOLISM. It usually refers to the coexistence of two or more subentities, i.e., ALCOHOLIC FATTY LIVER; ALCOHOLIC HEPATITIS; and ALCOHOLIC CIRRHOSIS.Quality-Adjusted Life Years: A measurement index derived from a modification of standard life-table procedures and designed to take account of the quality as well as the duration of survival. This index can be used in assessing the outcome of health care procedures or services. (BIOETHICS Thesaurus, 1994)Pregnancy Tests: Tests to determine whether or not an individual is pregnant.Contraception: Prevention of CONCEPTION by blocking fertility temporarily, or permanently (STERILIZATION, REPRODUCTIVE). Common means of reversible contraception include NATURAL FAMILY PLANNING METHODS; CONTRACEPTIVE AGENTS; or CONTRACEPTIVE DEVICES.Pregnancy Tests, Immunologic: Methods of detecting pregnancy by examining the levels of human chorionic gonadotropin (HCG) in plasma or urine.Urine: Liquid by-product of excretion produced in the kidneys, temporarily stored in the bladder until discharge through the URETHRA.Databases, Pharmaceutical: Databases devoted to knowledge about PHARMACEUTICAL PRODUCTS.Pharmacoepidemiology: The science concerned with the benefit and risk of drugs used in populations and the analysis of the outcomes of drug therapies. Pharmacoepidemiologic data come from both clinical trials and epidemiological studies with emphasis on methods for the detection and evaluation of drug-related adverse effects, assessment of risk vs benefit ratios in drug therapy, patterns of drug utilization, the cost-effectiveness of specific drugs, methodology of postmarketing surveillance, and the relation between pharmacoepidemiology and the formulation and interpretation of regulatory guidelines. (Pharmacoepidemiol Drug Saf 1992;1(1); J Pharmacoepidemiol 1990;1(1))Drug Utilization: The utilization of drugs as reported in individual hospital studies, FDA studies, marketing, or consumption, etc. This includes drug stockpiling, and patient drug profiles.Polypharmacology: The design or use of pharmaceutical agents that act on multiple targets or disease pathways.Protective Agents: Synthetic or natural substances which are given to prevent a disease or disorder or are used in the process of treating a disease or injury due to a poisonous agent.Herb-Drug Interactions: The effect of herbs, other PLANTS, or PLANT EXTRACTS on the activity, metabolism, or toxicity of drugs.Milk, HumanHepatitis, Chronic: INFLAMMATION of the LIVER with ongoing hepatocellular injury for 6 months or more, characterized by NECROSIS of HEPATOCYTES and inflammatory cell (LEUKOCYTES) infiltration. Chronic hepatitis can be caused by viruses, medications, autoimmune diseases, and other unknown factors.Clinical Trials, Phase I as Topic: Works about studies performed to evaluate the safety of diagnostic, therapeutic, or prophylactic drugs, devices, or techniques in healthy subjects and to determine the safe dosage range (if appropriate). These tests also are used to determine pharmacologic and pharmacokinetic properties (toxicity, metabolism, absorption, elimination, and preferred route of administration). They involve a small number of persons and usually last about 1 year. This concept includes phase I studies conducted both in the U.S. and in other countries.Chronic Disease: Diseases which have one or more of the following characteristics: they are permanent, leave residual disability, are caused by nonreversible pathological alteration, require special training of the patient for rehabilitation, or may be expected to require a long period of supervision, observation, or care. (Dictionary of Health Services Management, 2d ed)

Silibinin decreases prostate-specific antigen with cell growth inhibition via G1 arrest, leading to differentiation of prostate carcinoma cells: implications for prostate cancer intervention. (1/282)

Reduction in serum prostate-specific antigen (PSA) levels has been proposed as an endpoint biomarker for hormone-refractory human prostate cancer intervention. We examined whether a flavonoid antioxidant silibinin (an active constituent of milk thistle) decreases PSA levels in hormone-refractory human prostate carcinoma LNCaP cells and whether this effect has biological relevance. Silibinin treatment of cells grown in serum resulted in a significant decrease in both intracellular and secreted forms of PSA concomitant with a highly significant to complete inhibition of cell growth via a G1 arrest in cell cycle progression. Treatment of cells grown in charcoal-stripped serum and 5alpha-dihydrotestosterone showed that the observed effects of silibinin are those involving androgen-stimulated PSA expression and cell growth. Silibinin-induced G1 arrest was associated with a marked decrease in the kinase activity of cyclin-dependent kinases (CDKs) and associated cyclins because of a highly significant decrease in cyclin D1, CDK4, and CDK6 levels and an induction of Cip1/p21 and Kip1/p27 followed by their increased binding with CDK2. Silibinin treatment of cells did not result in apoptosis and changes in p53 and bcl2, suggesting that the observed increase in Cip1/p21 is a p53-independent effect that does not lead to an apoptotic cell death pathway. Conversely, silibinin treatment resulted in a significant neuroendocrine differentiation of LNCaP cells as an alternative pathway after Cip1/p21 induction and G1 arrest. Together, these results suggest that silibinin could be a useful agent for the intervention of hormone-refractory human prostate cancer.  (+info)

Stimulatory effects of silibinin and silicristin from the milk thistle Silybum marianum on kidney cells. (2/282)

The biochemical influence of flavonolignans from the milk thistle Silybum marianum has been tested on kidney cells of African green monkeys. Two nonmalignant cell lines were selected, with the focus of the work on the fibroblast-like Vero line. Proliferation rate, biosynthesis of protein and DNA, and the activity of the enzyme lactate dehydrogenase (as a measure of the cellular metabolic activity) were chosen as parameters for the effect of the flavonolignans. Silibinin and silicristin show remarkable stimulatory effects on these parameters, mainly in Vero cells; however, isosilibinin and silidianin proved to be inactive. In vitro experiments with kidney cells damaged by paracetamol, cisplatin, and vincristin demonstrated that administration of silibinin before or after the chemical-induced injury can lessen or avoid the nephrotoxic effects. The results warrant in vivo evaluations of the flavonolignan derivatives.  (+info)

Hepatitis C: epidemiology and review of complementary/alternative medicine treatments. (3/282)

Hepatitis C is emerging as a serious worldwide problem. In the United States the current mortality figures may triple in the next ten years, rivaling HIV. The disease has a latency of 10-30 years and symptoms or signs may not appear until cirrhosis is evident. Adequate diagnosis, including liver biopsy, is essential in assessing the current stage of the viral infection and the need for treatment. Hepatitis C may manifest as hepatic fibrosis, cirrhosis, hepatocellular carcinoma, lichen planus, glomerulonephritis, mixed cryoglobulinemia, or porphyria. The hepatic damage is due both to the cytopathic effect of the virus and the inflammatory changes secondary to immune activation. The use of the botanical components glycyrrhizin, catechin, silymarin and phytosterols, and the antioxidants N-acetylcysteine and vitamin E are reviewed for their efficacy in treating chronic hepatitis and affecting liver damage.  (+info)

Tissue distribution of silibinin, the major active constituent of silymarin, in mice and its association with enhancement of phase II enzymes: implications in cancer chemoprevention. (4/282)

Polyphenolic antioxidants are being identified as cancer preventive agents. Recent studies in our laboratory have identified and defined the cancer preventive and anticarcinogenic potential of a polyphenolic flavonoid antioxidant, silymarin (isolated from milk thistle). More recent studies by us found that these effects of silymarin are due to the major active constituent, silibinin, present therein. Here, studies are done in mice to determine the distribution and conjugate formation of systemically administered silibinin in liver, lung, stomach, skin, prostate and pancreas. Additional studies were then performed to assess the effect of orally administered silibinin on phase II enzyme activity in liver, lung, stomach, skin and small bowel. For tissue distribution studies, SENCAR mice were starved for 24 h, orally fed with silibinin (50 mg/kg dose) and killed after 0.5, 1, 2, 3, 4 and 8 h. The desired tissues were collected, homogenized and parts of the homogenates were extracted with butanol:methanol followed by HPLC analysis. The column eluates were detected by UV followed by electrochemical detection. The remaining homogenates were digested with sulfatase and beta-glucuronidase followed by analysis and quantification. Peak levels of free silibinin were observed at 0.5 h after administration in liver, lung, stomach and pancreas, accounting for 8.8 +/- 1.6, 4. 3 +/- 0.8, 123 +/- 21 and 5.8 +/- 1.1 (mean +/- SD) microg silibinin/g tissue, respectively. In the case of skin and prostate, the peak levels of silibinin were 1.4 +/- 0.5 and 2.5 +/- 0.4, respectively, and were achieved 1 h after administration. With regard to sulfate and beta-glucuronidate conjugates of silibinin, other than lung and stomach showing peak levels at 0.5 h, all other tissues showed peak levels at 1 h after silibinin administration. The levels of both free and conjugated silibinin declined after 0.5 or 1 h in an exponential fashion with an elimination half-life (t((1/2))) of 57-127 min for free and 45-94 min for conjugated silibinin in different tissues. In the studies examining the effect of silibinin on phase II enzymes, oral feeding of silibinin at doses of 100 and 200 mg/kg/day showed a moderate to highly significant (P < 0.1-0.001, Student's t-test) increase in both glutathione S-transferase and quinone reductase activities in liver, lung, stomach, skin and small bowel in a dose- and time-dependent manner. Taken together, the results of the present study clearly demonstrate the bioavailability of and phase II enzyme induction by systemically administered silibinin in different tissues, including skin, where silymarin has been shown to be a strong cancer chemopreventive agent, and suggest further studies to assess the cancer preventive and anticarcinogenic effects of silibinin in different cancer models.  (+info)

Silymarin suppresses TNF-induced activation of NF-kappa B, c-Jun N-terminal kinase, and apoptosis. (5/282)

Silymarin is a polyphenolic flavonoid derived from milk thistle (Silybum marianum) that has anti-inflammatory, cytoprotective, and anticarcinogenic effects. How silymarin produces these effects is not understood, but it may involve suppression of NF-kappa B, a nuclear transcription factor, which regulates the expression of various genes involved in inflammation, cytoprotection, and carcinogenesis. In this report, we investigated the effect of silymarin on NF-kappa B activation induced by various inflammatory agents. Silymarin blocked TNF-induced activation of NF-kappa B in a dose- and time-dependent manner. This effect was mediated through inhibition of phosphorylation and degradation of Iota kappa B alpha, an inhibitor of NF-kappa B. Silymarin blocked the translocation of p65 to the nucleus without affecting its ability to bind to the DNA. NF-kappa B-dependent reporter gene transcription was also suppressed by silymarin. Silymarin also blocked NF-kappa B activation induced by phorbol ester, LPS, okadaic acid, and ceramide, whereas H2O2-induced NF-kappa B activation was not significantly affected. The effects of silymarin on NF-kappa B activation were specific, as AP-1 activation was unaffected. Silymarin also inhibited the TNF-induced activation of mitogen-activated protein kinase kinase and c-Jun N-terminal kinase and abrogated TNF-induced cytotoxicity and caspase activation. Silymarin suppressed the TNF-induced production of reactive oxygen intermediates and lipid peroxidation. Overall, the inhibition of activation of NF-kappa B and the kinases may provide in part the molecular basis for the anticarcinogenic and anti-inflammatory effects of silymarin, and its effects on caspases may explain its role in cytoprotection.  (+info)

Synergy in a medicinal plant: antimicrobial action of berberine potentiated by 5'-methoxyhydnocarpin, a multidrug pump inhibitor. (6/282)

Multidrug resistance pumps (MDRs) protect microbial cells from both synthetic and natural antimicrobials. Amphipathic cations are preferred substrates of MDRs. Berberine alkaloids, which are cationic antimicrobials produced by a variety of plants, are readily extruded by MDRs. Several Berberis medicinal plants producing berberine were found also to synthesize an inhibitor of the NorA MDR pump of a human pathogen Staphylococcus aureus. The inhibitor was identified as 5'-methoxyhydnocarpin (5'-MHC), previously reported as a minor component of chaulmoogra oil, a traditional therapy for leprosy. 5'-MHC is an amphipathic weak acid and is distinctly different from the cationic substrates of NorA. 5'-MHC had no antimicrobial activity alone but strongly potentiated the action of berberine and other NorA substrates against S. aureus. MDR-dependent efflux of ethidium bromide and berberine from S. aureus cells was completely inhibited by 5'-MHC. The level of accumulation of berberine in the cells was increased strongly in the presence of 5'-MHC, indicating that this plant compound effectively disabled the bacterial resistance mechanism against the berberine antimicrobial.  (+info)

Inhibitory effect of a flavonoid antioxidant silymarin on benzoyl peroxide-induced tumor promotion, oxidative stress and inflammatory responses in SENCAR mouse skin. (7/282)

In this communication, we investigate the preventive effect of a flavonoid antioxidant, silymarin, on free radical-generating skin tumor promoting agent benzoyl peroxide (BPO)-induced tumor promotion, oxidative stress and inflammatory responses in SENCAR mouse skin. Topical application of silymarin at a dose of 6 mg prior to BPO resulted in a highly significant protection against BPO-induced tumor promotion in 7,12-dimethylbenz[a]anthracene-initiated SENCAR mouse skin. The preventive effect of silymarin was evident in terms of a 70% reduction (P < 0.001) in tumor incidence, a 67% reduction (P < 0.001) in tumor multiplicity and a 44% decrease (P < 0.001) in tumor volume/tumor. In oxidative stress studies, topical application of BPO resulted in 75, 87 and 61% depletion in superoxide dismutase (SOD), catalase and glutathione peroxidase (GPX) activities in mouse epidermis, respectively. These decreases in antioxidant enzyme activities were significantly (P < 0.005-0.001) reversed by pre-application of silymarin in a dose-dependent manner. The observed effects of silymarin were 18-66, 32-72 and 20-67% protection against BPO-induced depletion of SOD, catalase and GPX activity in mouse epidermis, respectively. Silymarin pre-treatment also resulted in a dose-dependent inhibition (35-87%, P < 0.05-0. 001) of BPO-induced lipid peroxidation in mouse epidermis. In inflammatory response studies, silymarin showed a strong inhibition of BPO-induced skin edema (62-85% inhibition, P < 0.001), myeloperoxidase activity (42-100% inhibition, P < 0.001) and interleukin-1alpha protein level in epidermis (36-81% inhibition, P < 0.001). These results, together with our other recent studies, suggest that silymarin could be useful in preventing a wide range of carcinogen and tumor promoter-induced cancers.  (+info)

Hepatotoxicity of tacrine: occurrence of membrane fluidity alterations without involvement of lipid peroxidation. (8/282)

Tacrine (THA), used in the treatment of Alzheimer's disease, is known to induce hepatotoxicity, the mechanisms of which remain to be fully established. We have previously shown that THA reduced intracellular glutathione concentration in rat hepatocytes in primary culture, thus pointing to a possible role for oxidative stress in THA toxicity. To test this, the effects of antioxidant molecules, namely, the flavonoids silibinin, silibinin dihydrogensuccinate, and silymarin, were evaluated on the toxicity of THA in cultured rat hepatocytes. This toxicity was investigated after a 24-h treatment over a concentration range from 0 to 1 mM, in the presence or absence of antioxidant (1 and 10 microM). We found that simultaneous treatment of hepatocytes with any of the antioxidants and THA remained ineffective on the lactate dehydrogenase release induced by THA. Then, the production of lipid-derived radicals (to estimate lipid peroxidation) was measured in THA (0.05-0.50 mM)-treated cells using a spin-trapping technique coupled to electron paramagnetic resonance (EPR) spectroscopy. No increase of the EPR signal was observed over the period of 30 min to 24 h. In contrast, treatment of cells with the spin label 12-doxyl stearic acid followed by EPR spectroscopy showed that THA (0.05 and 0.25 mM) rapidly increased hepatocyte membrane fluidity. Extracellular application of GM1 ganglioside (60 microM) both reversed this increase in fluidity and partially reduced lactate dehydrogenase release on THA exposure. In conclusion, this work indicates that early alterations of membrane fluidity, not resulting from lipid peroxidation, are likely to play an important role in the development of THA toxicity.  (+info)

  • The active constituent Silymarin protects the liver by strengthening the outer membranes of liver cells, preventing toxins from entering the cells. (
  • Besides its hepatoprotective principle, silymarin is a potent chemopreventive agent ( 13 , 14 , 15 ). (
  • Silymarin, as the plant active ingredient of Carsil has well documented benefits with hepatoprotective and antioxidative action, with a consolidating effect on the cell membrane, thus protecting the liver from harmful impacts and facilitating the recovery of the impaired liver cells. (
  • These data show that even higher-than-normal doses of silymarin don't significantly reduce ALT levels for patients with HCV,' said Reddy, noting that the doses used in the trial were three and five times higher than the customary dose. (
  • Silymarin strongly prevents photocarcinogenesis, and significantly prevented melanin production. (
  • Silymarin also blocked NF-κB activation induced by phorbol ester, LPS, okadaic acid, and ceramide, whereas H 2 O 2 -induced NF-κB activation was not significantly affected. (
  • Because silymarin has been described to be an antioxidant with anti-inflammatory, cytoprotective, and anticarcinogenic effects, we tested the hypothesis that these effects are mediated through its modulation of activation of NF-κB, members of the MAPK, and caspase-mediated apoptosis. (
  • Silymarin and skin cancer prevention: anti-inflammatory, antioxidant and immunomodulatory effects (review). (
  • This review does not aim to replace future prospective trials aiming to provide the 'final' evidence of the efficacy of silymarin. (
  • A study published in Pharmaceutical Research in September 2008 identified the strong efficacy of silymarin in prostate cancer prevention and intervention, as reported in previous studies. (
  • We conclude that available evidence suggests that silymarin may play a role in the therapy of (alcoholic) liver cirrhosis. (
  • In the group receiving APAP plus silymarin, levels of lipid peroxidation and serum enzyme activities remained within the control values at any time studied. (
  • Silymarin suppressed the TNF-induced production of reactive oxygen intermediates and lipid peroxidation. (
  • By all indications, silymarin is no more effective at treating hepatitis C related chronic liver disease, in those who failed standard therapy with interferon, than a placebo,' said K. Rajender Reddy, MD, professor of Medicine and medical director of Liver Transplantation at Penn Medicine, and senior author of the study. (
  • Participants were randomly assigned to receive 420mg silymarin, 700mg silymarin or a matching placebo administered three times/week for 24 weeks, a standard duration of treatment. (
  • Silymarin scavenges free radicals and inhibits aldose reductase - an enzyme which causes sugar deposits in the eyes of diabetics. (
  • 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. (
  • The four-year survival rate was 58 percent in the silymarin group with the most pronounced reduced death rate in the alcoholic cirrhosis subgroup. (
  • The study included three groups of rats: Control non-treated group, ALI group (intra-tracheal HCl injected), and silymarin treated ALI group. (
  • 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. (
  • Silymarin is also used to complement the therapy of viral hepatitis. (
  • Silymarin, an extract of milk thistle commonly used to treat chronic liver disease by millions of people around the World, does not offer significant improvements for patients, according to a new study conducted by a nationwide group of researchers including faculty at the Perelman School of Medicine at the University of Pennsylvania. (
  • The active component of Carsil, Silymarin stabilizes the cell membrane of the liver and stimulates protein synthesis, which restores the functions of the damaged cells and protects the liver parenchyma from destructive action of noxae. (
  • How silymarin mediates its anticarcinogenic effects is not fully understood, but it has been shown that some of the effects are mediated through inhibition of receptor tyrosine kinases ( 16 ), cyclin-dependent kinases ( 17 , 18 ), TNF mRNA expression ( 19 ), and ornithine decarboxylase activity ( 13 ). (
  • Therefore, the objective of this review is to assess the clinical efficacy and safety of silymarin by application of systematic approach. (
  • 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)-κB. (
  • This RFA is a one-time solicitation to request for applications to perform multi-site Phase I/II clinical trials of silymarin for liver diseases. (
  • The National Center for Complementary and Alternative Medicine (NCCAM), in collaboration with the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the National Institutes of Health, of the U.S Department of Health and Human Services is seeking applications to perform Phase I/II clinical trials with silymarin for chronic liver diseases. (
  • Silymarin benefits have been documented by various clinical trials and over 2,000 years of use as a supplement. (
  • In the clinical trial 170 patients, 91 of them alcoholics with liver cirrhosis were given 140 mg silymarin three times a day for 41 months. (
  • How silymarin produces these effects is not understood, but it may involve suppression of NF-κB, a nuclear transcription factor, which regulates the expression of various genes involved in inflammation, cytoprotection, and carcinogenesis. (
  • 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. (
  • It is believed to be one of the reasons why silymarin is able to protect the liver. (
  • Silymarin ameliorated the histopathological lung injury with further up-regulation of Nrf-2 and HO-1 mRNA and decreased the inflammatory and fibrotic parameters together with up-regulation of the anti-apoptotic and the proliferation parameters. (