Human acyl-CoA: Cholesterol acyltransferase (hACAT) inhibitory activities of triterpenoids from roots of Glycine max (L.) Merr.

Abstract

Eight triterpenoids, six lanostanes 1-6, one lupenane 7, and one oleanane 8, were isolated by bioactivity-guided fractionation of the ethylacetate extract from roots of Glycine max (L.) Merr. All isolated compounds were examined for their inhibitory activities against human ACAT-1 (hACAT-1) and human ACAT-2 (hACAT-2). Among them, three triterpenoids showed potent hACAT inhibitory activities, (24R)-ethylcholest-5-ene-3,7-diol (1) and 3 beta-hydroxylup-20(29)-en-28-oic acid (7) exhibited more potent inhibitory activity against hACAT-1 (1: IC50 = 25.0 +/- 1.2 and 7: IC50 = 11.5 +/- 0.4 mu M) than hACAT-2 (1: IC50 = 102.0 +/- 5.4 and 7: IC50 = 33.9 +/- 3.7 mu M), respectively. Interestingly, 5 alpha,8 alpha-epidioxy-24(R)-methylcholesta-6,22-diene-3 beta-ol (4) has proven to be a specific inhibitor against hACAT-1 (IC50 = 38.7 +/- 0.8 mu M) compared to hACAT-2 (IC50 > 200). In conclusion, this is the first study to demonstrate that triterpenoids of G. max have potent inhibitory activities against hACAT-1 and hACAT-2.