Search

Silymarin has long been used as a hepatoprotective remedy. Chronic toxicity studies in rodents have confirmed that silymarin has a very low toxicity. These data support its history as a safe medication in hepatic diseases. In the last years, several studies expanded our understanding of the pharmacology of silymarin and its molecular mechanisms of action. These new insights may affect the handling of silymarin in clinical studies and daily practice. Additionally, scientific knowledge in hepatology is constantly evolving with, particularly, an increase in the field of non-alcoholic fatty liver disease which is considered today as the most frequent liver disease worldwide. In this review, we will describe scientific evidence for the effectiveness of silymarin in hepatic disorders. We will focus on silymarin’s pharmacological effects in non-alcoholic fatty liver disease and on its well described effects in alcoholic liver disease and acute intoxications, e.g. with Amanita species. We will discuss the relevance of pharmacological data as a function of doses or concentrations required for a given effect and of concentrations achieved in the target tissues. Many pharmacological effects of silymarin can be attributed to effects downstream or upstream of its antioxidative and membrane-stabilizing properties. However, despite promising new experimental and clinical data further clinical studies are required including long-term observations and the application of hard clinical endpoints such as survival rates, to further support silymarin’s use for the treatment of hepatic diseases.

Background Silymarin derived from the milk thistle plant “Silybum marianum” is composed of four major flavonolignans. Clinical as well as experimental studies indicate hepatoprotective effects of silymarin. However, the underlying mechanisms are only incompletely understood. The aim of this study was to assess the effect of oral administration of a defined silymarin extract in the model of acute carbon tetrachloride (CCl4) induced liver injury. Methods A single dose of a silymarin extract (SE; 20 or 100 mg/kg body weight) was given to rats by oral gavage. Subsequently, rats were injected with a single dose of CCl4 (2 ml/kg body weight). Results After 24h, analysis of liver to body weight ratio, serum levels of transaminases and histological analysis revealed a marked liver damage which was inhibited by SE in a dose dependent manner. CCl4-induced expressions of pro-inflammatory and pro-fibrogenic genes were significantly reduced in SE treated rats. Molecular analysis revealed that SE reduced the expression of the pro-inflammatory chemokine MCP-1, the pro-fibrogenic cytokine TGF-beta as well as collagen I in isolated human hepatic stellate cells (HSC), which are the key effector cells of hepatic fibrosis. Conclusion Oral administration of the tested silymarin extract inhibited hepatocellular damage in a model of acute liver injury. Moreover, we newly found that the silymarin extract had direct effects on pro-inflammatory and pro-fibrogenic gene expression in HSCs in vitro. This indicates that direct effects on HSC also contribute to the in vivo hepatoprotective effects of silymarin, and further promote its potential as anti-fibrogenic agent also in chronic liver disease.