Inhibitory effects of Polygonum cuspidatum water extract (PCWE) and its component rasveratrol on acyl-coenzyme A-cholesterol acyltransferase activity for cholesteryl ester synthesis in HepG2 cells

The pharmacological effects of Polygonum cuspidatum water extract (PCWE) on lipid biosynthesis were investigated in cultured human hepatocyte HepG2 cells. The addition of PCWE (5 and 20 μg/ml), which had no effect on cell proliferation and cellular protein content, caused a marked decrease in the cellular cholesterol content, particularly, the cholesteryl ester content following 24 h of incubation. The incorporation of ¹⁴C-oleate into the cellular cholesteryl ester fraction was also reduced remarkably during incubation for 6 and 24 h. The effect of PCWE on acyl-coenzyme A-cholesterol acyltransferase (ACAT) activity were studied in vitro to explore the mechanism by which PCWE inhibits cholesterol ester formation. The data confirmed that PCWE, in a dose dependent manner, remarkably inhibits ACAT activity. Among the main active chemicals of P. cuspidatum, resveratrol, a kind of flavonoid, decreased ACAT activity in a dose-dependent manner from the level of 10 ^-3 M. Theses results strongly suggest that PCWE reduces the cholesteryl ester formation in human hepatocytes by inhibiting ACAT.