Antidiabetic principles of natural medicines. III. Structure-related inhibitory activity and action mode of oleanolic acid glycosides on hypoglycemic activity

1998

REP.G2141

Structure-activity relations of oleanolic acid glycosides (oleanolic acid 3-O-glucuronide and momordin Ic from fruits of Kochia scoparia) were examined with regard to their inhibitory effects on the increase of serum glucose in oral glucose-loaded rats and their mechanism of action. Both a 3-O-monodesmoside structure and a 28-carboxyl group were confirmed to be essential for such activity; the 3-O-glucuronide was more potent than 3-O-glucoside. A 28-ester glucoside moiety and 6'-methyl ester of the glucuronide moiety decreased such activity. Oleanolic acid 3-O-glucuronide and momordin Ic, both of which inhibited the increase of serum glucose in orally glucose-loaded rats, did not lower serum glucose in normal or intraperitoneally glucose-loaded rats, or in alloxan-induced diabetic mice. These glycosides were found to suppress gastric emptying in rats, and to inhibit glucose uptake in the rat small intestine in vitro. These results indicate that oleanolic acid 3-O-glucuronide and momordin Ic, given orally, have neither insulin-like activity nor insulin-releasing activity. They exhibit their hypoglycaemic activity by suppressing the transfer of glucose from the stomach to the small intestine and by inhibiting glucose transport at the brush border of the small intestine.

v.46(9):1399-1403, CHEMICAL AND PHARMACEUTICAL BULLETIN

Research > Published Articles