HYPOCHOLESTEROLEMIC PROPERTIES OF PLANT INDOLES - INHIBITION OF ACYL-COA-CHOLESTEROL ACYLTRANSFERASE ACTIVITY AND REDUCTION OF SERUM LDL/VLDL CHOLESTEROL LEVELS BY GLUCOBRASSICIN DERIVATIVES

Studies were undertaken to investigate the effects of the plant compound indole-3-carbinol (I3C) and its acid condensation products, which are generated in the stomach following ingestion of I3C, on cholesterol homeostasis in mice. Individual acid condensation products were synthesized and purified by HPLC. In vitro experiments revealed that several of the acid condensation products effectively inhibited the enzyme acyl-CoA:cholesterol acyltransferase (ACAT), which is responsible for the conversion of free cholesterol to the cholesteryl ester, at micromolar concentrations. Since the inhibition of ACAT in vivo should reduce serum cholesterol levels, I3C was administered to mice, and the effects on serum cholesterol levels were evaluated. Total serum cholesterol levels were elevated by 29% in mice provided a 3% cholesterol-supplemented diet, but this elevation was attenuated significantly (P less than or equal to 0.05) by approximately 50% when I3C (100 mg/kg/day) was added to this diet. This effect of I3C was entirely on low density lipoprotein (LDL)/very low density lipoprotein (VLDL) cholesterol, which was lowered significantly (P less than or equal to 0.05) by approximately 30%. In summary, I3C lowered serum LDL/VLDL cholesterol levels in mice, and this effect was likely mediated by the inhibition of ACAT by some of the acid condensation products of I3C. These results provide a possible mechanism by which I3C-rich vegetables lower serum cholesterol levels.