Inhibitory Effects of Oren-Gedoku-to and its Components on Cholesteryl Ester Synthesis in Cultured Human Hepatocyte HepG2 Cells: Evidence from the Cultured Hep2G Cells and In Vitro Assay of ACAT

Abstract

The pharmacological effects of Oren-gedoku-to (OGT), a Japanese-Chinese traditional herbal medicinal mixture, on lipid biosynthesis were investigated in cultured human hepatocyte HepG2 cells. The addition of OGT (0.5 and 4.2 mg/ml), which had no effect on cell proliferation and cellular protein content, caused a marked decrease in the cellular cholesterol content, particularly cholesteryl ester content following 24 h incubation. The incorporation of ¹⁴ C-oleate into cellular cholesteryl ester fraction was also reduced remarkably during incubation for 6 and 24 h. The effects of OGT, its components and its main active chemicals on acyl-coenzyme A:cholesterol acyltransferase (ACAT) activity were studied in vitro to explore the mechanism by which OGT inhibits cholesteryl ester formation. The data confirmed that OGT, in a dose-dependent manner, and its components (Scutellaria baicalensis, Coptis japonica, Gardenia jasminoides and Phelloden-dron amurense) remarkably inhibit ACAT activity. Among the main active chemicals of OGT, baicalein, a kind of flavonoid, decreased ACAT activity in a dose-dependent fashion from the level of 10^-6M. These results strongly suggest that OGT reduces the cholesteryl ester formation in human hepatocytes by inhibiting ACAT, and that baicalein may, in part, be responsible for ACAT inhibition.

key words

Herbal medicine - Oren-gedoku-to - Scutellaria baicalensis - Coptis japonica - Gardenia jasminoides - Phellodendron amurense - baicaleine - cholesteryl ester - ACAT - HepG2 cells - ¹⁴ C-oleic acid