Antioxidant evaluation of Eysenhardtia species (Fabaceae): relay synthesis of 3-O-Acetyl-11alpha,12alpha-epoxy-oleanan-28,13beta-olide isolated from E. platycarpa and its protective effect in experimental diabetes.

The antioxidant activities of plant extracts from Eysenhardtia platycarpa, E. punctata, and E. subcoriacea (Fabaceae) species, used in Mexican traditional medicine for the treatment of diabetes complications, were analyzed in a rat pancreas homogenate model. Methanolic extracts of E. platycarpa, E. punctata, and E. subcoriacea protected the pancreatic homogenate from 2,2-azo-bis(2-amidinopropane)dihydrochloride (AAPH)-induced damage. The inhibitory effect was dose-dependent at concentrations of 10-1000 ppm and correlated with 1,1 diphenyl-2-picrylhydrazyl (DDPH) radical scavenger capacity. 3-O-Acetyl-11alpha,12alpha-epoxy-oleanan-28,13beta-olide (1, EC(50)=21.2+/-2.2 microM), (+)-catechin (2, EC(50)=7.4+/-1.1 microM), and (+)-catechin 3-O-beta-D-galactopyranoside (3, EC(50)=11.5+/-1.5 microM), natural constituents isolated from the branches of E. platycarpa, displayed significant antioxidant activity. Compounds 1 and 2 significantly increased (p<0.001) the pancreatic glutathione (GSH) concentration alone and in combination with AAPH treatment. Compound 1 was obtained from oleanolic acid by relay synthesis via acetylation, bromo-lactonization, dehydrobromination, and oxidation, and its antioxidant effect was evaluated on streptozotocin (STZ)-induced diabetic rats. On its own, 1 at a dose of 100 mg/kg b. wt. (i.p.) for 5 d significantly increased the activities of glutathione peroxidase (GSHPx) and catalase (CAT). Simultaneous treatment of 1 (100 mg/kg b. wt.) and STZ significantly reduced the pancreatic thiobarbituric acid reactive substances (TBARS) concentration together with a significant increase in the activities of GSHPx and CAT, preventing hyperglycemia induced by STZ after 5 d of treatment. The present study demonstrates the antioxidant and antihyperglycemic activities of compound 1 isolated from Eysenhardtia species used in traditional medicine.