Structure-related inhibitory activity of oleanolic acid glycosides on gastric emptying in mice.
We examined the effects of various oleanolic acid oligoglycosides obtained from traditional herbs on gastric emptying in non-nutrient meal- or nutrient meal-loaded mice. Test samples were given orally to fasted mice 0.5 h before loading of test meals. Oleanolic acid 3-O-monodesmosides [oleanolic acid 3-O-glucuronide (3, 12.5-50 mg/kg), momordin Ic (4, 25 and 50 mg/kg), momordin I (6, 12.5-50 mg/kg), and 28-O-deglucosyl-chikusetsusaponins IV (8, 12.5-50 mg/kg) and V (10, 50 mg/kg)] were found to show inhibitory effects on gastric emptying in 1.5% CMC-Na test meal-loaded mice. 4, 6, and 8 also inhibited gastric emptying in mice given 40% glucose test meal, milk test meal, and 60% ethanol test meal. 3 inhibited gastric emptying in mice given milk test meal or 60% ethanol test meal, but lacked significant inhibition in 40% glucose test meal-loaded mice. 10 (50 mg/kg) also slightly inhibited gastric emptying in milk test meal-loaded mice, but lacked the significant inhibition in mice given 40% glucose or 60% ethanol test meal. Whereas oleanolic acid 3,28-0-bisdesmosides [momordin IIc (5), chikusetsusaponins IV (7) and V (9)], oleanolic acid 28-O-monodesmoside [compound O (2)], and their common aglycon [oleanolic acid (1)] showed no such effects at dose of 50 mg/kg. 28-O-Deglucosyl-chikusetsusaponin V (10) showed a little inhibition in these experiments. These results indicate that both the 3-O-monodesmoside structure and 28-carboxyl group were confirmed to be essential for such activity, and the 28-ester glucoside moiety and 2'-O-beta-D-glucopyranoside moiety reduce the activity.
Matsuda
H
H
Kyoto Pharmaceutical University, Japan.
Li
Y
Y
Murakami
T
T
Yamahara
J
J
Yoshikawa
M
M
D000818:Animals; D005746:Gastric Emptying / Q000187:drug effects*; D005947:Glucose / Q000378:metabolism; D006634:Histamine H1 Antagonists / Q000378:metabolism; D008297:Male; D051379:Mice; D008892:Milk / Q000378:metabolism; D008956:Models, Chemical; D009828:Oleanolic Acid / Q000031:analogs & derivatives / Q000737:chemistry*; D013329:Structure-Activity Relationship
D006634:Histamine H1 Antagonists; C408362:momordin I (Oleanolic Acid); D009828:Oleanolic Acid; D005947:Glucose