|The efficacy of Silybum marianum (L.) Gaertn. (silymarin) in the treatment of type II diabetes: a randomized, double-blind, placebo-controlled, clinical trial.
Oxidative stresses are increasingly implicated in the pathogenesis of diabetic complications which may either cause direct pancreatic beta-cell damage or lead to metabolic abnormalities that can induce or aggravate diabetes. The valuable effect of antioxidant nutrients on the glycemic control of diabetic patients has been reported in experimental and clinical studies. The present study was designed to investigate the effects of the herbal medicine, Silybum marianum seed extract (silymarin), which is known to have antioxidant properties on the glycemic profile in diabetic patients. A 4-month randomized double-blind clinical trial was conducted in 51 type II diabetic patients in two well-matched groups. The first group (n = 25) received a silymarin (200 mg) tablet 3 times a day plus conventional therapy. The second group (n = 26) received the same therapy but a placebo tablet instead of silymarin. The patients were visited monthly and glycosylated hemoglobin (HbA(1)c), fasting blood glucose (FBS), insulin, total cholesterol, LDL and HDL, triglyceride, SGOT and SGPT levels were determined at the beginning and the end of the study. The results showed a significant decrease in HbA(1)c, FBS, total cholesterol, LDL, triglyceride SGOT and SGPT levels in silymarin treated patients compared with placebo as well as with values at the beginning of the study in each group. In conclusion, silymarin treatment in type II diabetic patients for 4 months has a beneficial effect on improving the glycemic profile.
Phytother Res. 2006 Dec;20(12):1036-9
The safety and efficacy of a silymarin and selenium combination in men after radical prostatectomy - a six month placebo-controlled double-blind clinical trial.
Silymarin, a milk thistle flavonolignan mixture, has anti-proliferative and anti-angiogenic activities in xenografts of human prostate cancer (PCa). Low dietary selenium on the other hand has been associated with increased incidence of PCa. The purpose of the current trial was to determine whether a daily administration of a silymarin and selenium (SM-Se) combination for 6 months would alter basic clinical chemistry and oxidative stress markers, and improve the quality of life score (QoL) in men after radical prostatectomy (RP). Thirty seven participants, 2-3 months after RP, were randomly assigned to receive 570 mg of silymarin and 240 µg of selenium as selenomethionine (n = 19, SM-Se group) or placebo (n = 18, Placebo group) daily for six months. Both groups had similar clinical and demographic characteristics. Physical examination, QoL score, haematology, basic clinical chemistry and oxidative stress markers, selenium and testosterone levels, antioxidant status were evaluated at baseline, at 3 and 6 months. The six months administration of silymarin and selenium improved the QoL score, decreased low density lipoproteins (LDL) and total cholesterol and, increased serum selenium levels. The combination had no effect on blood antioxidant status and no influence on testosterone level. No adverse events were recorded. No improvement was found in the placebo group. The selected combination of silymarin and selenium significantly reduced two markers of lipid metabolism known to be associated with PCa progression, LDL and total cholesterol in the blood of men after RP. This suggests that this combination may be effective in reducing PCa progression.
Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2010 Sep;154(3):239-44
Multitargeted therapy of cancer by silymarin.
Silymarin, a flavonolignan from milk thistle (Silybum marianum) plant, is used for the protection against various liver conditions in both clinical settings and experimental models. In this review, we summarize the recent investigations and mechanistic studies regarding possible molecular targets of silymarin for cancer prevention. Number of studies has established the cancer chemopreventive role of silymarin in both in vivo and in vitro models. Silymarin modulates imbalance between cell survival and apoptosis through interference with the expressions of cell cycle regulators and proteins involved in apoptosis. In addition, silymarin also showed anti-inflammatory as well as anti-metastatic activity. Further, the protective effects of silymarin and its major active constituent, silibinin, studied in various tissues, suggest a clinical application in cancer patients as an adjunct to established therapies, to prevent or reduce chemotherapy as well as radiotherapy-induced toxicity. This review focuses on the chemistry and analogues of silymarin, multiple possible molecular mechanisms, in vitro as well as in vivo anti-cancer activities, and studies on human clinical trials.
Cancer Lett. 2008 Oct 8;269(2):352-62.
Silymarin attenuated the amyloid plaque burden and improved behavioral abnormalities in an Alzheimer’s disease mouse model.
Alzheimer’s disease (AD) is characterized by progressive cognitive impairment and the formation of senile plaques. Silymarin, an extract of milk thistle, has long been used as a medicinal herb for liver diseases. Here we report marked suppression of amyloid β-protein (Aβ) fibril formation and neurotoxicity in PC12 cells after silymarin treatment in vitro. In vivo studies had indicated a significant reduction in brain Aβ deposition and improvement in behavioral abnormalities in amyloid precursor protein (APP) transgenic mice that had been preventively treated with a powdered diet containing 0.1% silymarin for 6 months. The silymarin-treated APP mice also showed less anxiety than the vehicle-treated APP mice. These behavioral changes were associated with a decline in Aβ oligomer production induced by silymarin intake. These results suggest that silymarin is a promising agent for the prevention of AD.
Biosci Biotechnol Biochem. 2010 Nov 23;74(11):2299-306
Silymarin retards the progression of alcohol-induced hepatic fibrosis in baboons.
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.
J Clin Gastroenterol. 2003 Oct;37(4):336-9
Silymarin protects liver against toxic effects of anti-tuberculosis drugs in experimental animals.
The first line anti-tuberculosis drugs isoniazid (INH), rifampicin (RIF) and pyrazinamide (PZA) continues to be the effective drugs in the treatment of tuberculosis, however, the use of these drugs is associated with toxic reactions in tissues, particularly in the liver, leading to hepatitis. Silymarin, a standard plant extract with strong antioxidant activity obtained from S. marianum, is known to be an effective agent for liver protection and liver regeneration. The aim of this study was to investigate the protective actions of silymarin against hepatotoxicity caused by different combinations of anti-tuberculosis drugs. Male Wistar albino rats weighing 250-300 g were used to form 6 study groups, each group consisting of 10 rats. Animals were treated with intra-peritoneal injection of isoniazid (50 mg/kg) and rifampicin (100 mg/kg); and intra-gastric administration of pyrazinamid (350 mg/kg) and silymarin (200 mg/kg). Hepatotoxicity was induced by a combination of drugs with INH+RIF and INH+RIF+PZA. Hepatoprotective effect of silymarin was investigated by co-administration of silymarin together with the drugs. Serum biochemical tests for liver functions and histopathological examination of livers were carried out to demonstrate the protection of liver against anti-tuberculosis drugs by silymarin. Treatment of rats with INH+RIF or INH+RIF+PZA induced hepatotoxicity as evidenced by biochemical measurements: serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) activities and the levels of total bilirubin were elevated, and the levels of albumin and total protein were decreased in drugs-treated animals. Histopathological changes were also observed in livers of animals that received drugs. Simultaneous administration of silymarin significantly decreased the biochemical and histological changes induced by the drugs. The active components of silymarin had protective effects against hepatotoxic actions of drugs used in the chemotherapy of tuberculosis in animal models. Since no significant toxicity of silymarin is reported in human studies, this plant extract can be used as a dietary supplement by patients taking anti-tuberculosis medications.
Nutr Metab (Lond). 2008 Jul 5;5:18
An updated systematic review with meta-analysis for the clinical evidence of silymarin.
The potential benefit of silymarin (special extract from the fruits of Silybum marianum) in the treatment of liver diseases remains a controversial issue. For this systematic review electronic databases identified 65 papers for the search terms silymarin, silibinin, silicristin or milk thistle and clinical trial. Only 19 complied with the criteria ’double-’ or ‘single-blind’. These publications were analysed from a clinical point of view and meta-analytic calculations were performed. The clinical evidence of a therapeutic effect of silymarin in toxic liver diseases is scarce. There is no evidence of a favourable influence on the evolution of viral hepatitis, particularly hepatitis C. In alcoholic liver disease, comparing with placebo, aspartate aminotransferase was reduced in the silymarin-treated groups (p = 0.01) while alkaline phosphatase was not. In liver cirrhosis, mostly alcoholic, total mortality was 16.1% with silymarin vs. 20.5% with placebo (n.s.); liver-related mortality was 10.0% with silymarin vs. 17.3% with placebo(p = 0.01). Based on the available clinical evidence it can be concluded - concerning possible risks /probable benefits - that it is reasonable to employ silymarin as a supportive element in the therapy of Amanita phalloides poisoning but also (alcoholic and grade Child ‘A’) liver cirrhosis. A consistent research programme, consolidating existing evidence and exploring new potential uses,would be very welcome.
Forsch Komplementmed. 2008 Feb;15(1):9-20