Effect of Silibinin on biliary lipid composition. Experimental and clinical study

The effect of Silymarin, a natural flavonoid, on biliary lipid composition, was studied in rats and humans. Bile flow, biliary cholesterol, phospholipid and total bile salt concentrations were measured in 23 control rats and in 27 rats treated with Silibinin, the active component of Silymarin, at the dose of 100 mg/kg body weight i.p. (n = 21) or 50 mg/kg body weight i.p. (n = 6) for 7 days. Biliary cholesterol and phospholipid concentrations were significantly reduced after the higher Silibinin dose (60.9 and 72.9% of the control values), whereas bile flow and biliary total bile salt concentration were unchanged. After the lower Silibinin dose all parameters remained unchanged. Total liver cholesterol content was not affected by Silibinin. On the other hand, in vitro determination of rat liver microsomal 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase activity showed a significant dose-dependent inhibition by Silibinin (0.5-8 mg/kg). Biliary lipid composition was also assayed in four gallstone and in 15 cholecystectomized patients before and after Silymarin (420 mg per day for 30 days) or placebo administration. In both groups, biliary cholesterol concentrations were reduced after Silymarin treatment and the bile saturation index significantly decreased accordingly. These data suggest that Silibinin-induced reduction of biliary cholesterol concentration both in humans and in rats might be, at least in part, due to a decreased synthesis of liver cholesterol.