INHIBITORY EFFECTS OF OREN-GEDOKU-TO AND ITS COMPONENTS ON CHOLESTERYL ESTER SYNTHESIS IN CULTURED HUMAN HEPATOCYTE HEPG2 CELLS - EVIDENCE FROM THE CULTURED HEPG2 CELLS AND IN-VITRO ASSAY OF ACAT

The pharmacological effects of Oreg-gedoku-to (OGT), a Japanese-Chines e traditional herbal medicinal mixture, on lipid biosynthesis were inv estigated in cultured human hepatocyte HepG2 cells. The addition of OG T (0.5 and 4.2 mg/ml), which had no effect on cell proliferation and c ellular protein content, caused a marked decrease in the cellular chol esterol content, particularly cholesteryl ester content following 24 h incubation. The incorporation of C-14-oleate into cellular cholestery l ester fraction was also reduced remarkably during incubation for 6 a nd 24 h. The effects of OGT, its components and its main active chemic als on acyl-coenzyme A:cholesterol acyltransferase (ACAT) activity wer e studied in vitro to explore the mechanism by which OGT inhibits chol esteryl ester formation. The data confirmed that OGT, in a dose-depend ent manner, and its components (Scutellaria baicalensis, Coptis japoni ca, Gardenia jasminoides and Phellodendron amurense) remarkably inhibi t ACAT activity. Among the main active chemicals of OCT, baicalein, a kind of flavonoid, decreased ACAT activity in a dose-dependent fashion from the level of 10(-6) M. These results strongly suggest that OCT r educes the cholesteryl ester formation in human hepatocytes by inhibit ing ACAT, and that baicalein may, in part, be responsible for ACAT inh ibition.