Oleanane-Type Triterpenoids of Aceriphyllum rossii and Their Diacylglycerol Acyltransferase-Inhibitory Activity

Six known triterpenoid compounds, 3-oxoolean-12-en-27-oic acid ( 1 ), gypsogenic acid ( 2 ), 3 α -hydroxyolean-12-en-27-oic acid ( 3 ), 3 β -hydroxyolean-12-en-27-oic acid ( 4 ), aceriphyllic acid A ( 5 ), and oleanolic acid ( 6 ), were isolated from the roots of Aceriphyllum rossii . Their chemical structures were determined by comparison with available 1 H-NMR and 13 C-NMR data on known compounds. All the isolated compounds were evaluated for inhibitory activity against human diacylglycerol acyltransferases 1 and 2. Most of the isolates exhibited a better inhibitory activity against diacylglycerol acyltransferase 2 (IC 50 : 11.6–44.2 µM) than against diacylglycerol acyltransferase 1 (IC 50 : 22.7–119.5 µM). In particular, compounds 1 and 5 showed strong inhibition efficacy towards diacylglycerol acyltransferases 1 and 2, and appeared to act competitively against oleoyl-CoA in vitro. The results also indicated that both compounds reduced newly synthesized triacylglycerol in HuTu80 and HepG2 cells. Oral administration of compound 1 significantly reduced postprandial triacylglycerol in mice following an oral lipid challenge. In conclusion, the current study indicates that compound 1 suppresses both de novo triacylglycerol biosynthesis and resynthesis through the inhibition of diacylglycerol acyltransferase activity, and therefore may be a useful agent for treating diseases associated with a high triacylglycerol level.