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 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 14C-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 Phellodendron 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(-6)M. 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.
Yotsumoto
H
H
Department of Applied Biological Sciences, Saga University, Japan.
Yanagita
T
T
Yamamoto
K
K
Ogawa
Y
Y
Cha
J Y
JY
Mori
Y
Y
D002250:Carbon Radioisotopes; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002784:Cholesterol / Q000378:metabolism; D002788:Cholesterol Esters / Q000096:biosynthesis*; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D010946:Plants, Medicinal / Q000737:chemistry*; D002785:Sterol O-Acyltransferase / Q000037:antagonists & inhibitors / Q000378:metabolism*
D002250:Carbon Radioisotopes; D002788:Cholesterol Esters; D004365:Drugs, Chinese Herbal; D004791:Enzyme Inhibitors; C061676:oren gedoku to; D002784:Cholesterol; D002785:Sterol O-Acyltransferase