No abstract

Among antihyperglycemic drugs used for treating diabetes, α-glucosidase inhibitors generate the least adverse effects. This contribution aimed to evaluate the potential antidiabetic activity of Rumex crispus L. by testing its in vitro α-glucosidase inhibition and in vivo antihyperglycemic effects on rats with streptozotocin (STZ)-induced diabetes. Better inhibition of α-glucosidase was found with the methanol extract versus the n-hexane and dichloromethane extracts. The methanol extract of the flowers (RCFM) was more effective than that of the leaves (RCHM), with an IC50 of 7.3 ± 0.17 μg/mL for RCFM and 112.0 ± 1.23 μg/mL for RCHM. A bioactive fraction (F89s) also showed good α-glucosidase inhibition (IC50 = 3.8 ± 0.11 μg/mL). In a preliminary study, RCHM and RCFM at 150 mg/kg and F89s at 75 mg/kg after 30 days showed a significant effect on hyperglycemia, reducing glucose levels (82.2, 80.1, and 84.1%, respectively), and improved the lipid, renal, and hepatic profiles of the rats, comparable with the effects of metformin and acarbose. According to the results, the activity of R. crispus L. may be mediated by a diminished rate of disaccharide hydrolysis, associated with the inhibition of α-glucosidase. Thus, R. crispus L. holds promise for the development of auxiliary drugs to treat diabetes mellitus.

The aim of the present study was to synthesize isoflavone-enaminones 3a-c and 7-alkoxy-isoflavones 4a-c, evaluate their inhibition of a-glucosidase, and analyze the bioisosteric effect of the presence versus absence of aromatic moieties in these benzopyran derivatives. All the test compounds exhibited a greater inhibition of a-glucosidase than the positive control acarbose. The series of isoflavones 3a-c and 4a-c showed a higher inhibitory activity (IC50 = 6.3 - 87.6 µM) than the parental 7-hydroxyisoflavones 2a-c (IC50 = 109.4 - 173.2 µM), suggesting that the attachment of a 4’-chloroacetophenone moiety to the 7-hydroxyl group of 2a-c is an efficient way to increase the inhibition of a-glucosidase. Furthermore, the aromatic moieties of the series of compounds 3 and 4 enhance the inhibitory activity by hydrophobic effects according to docking calculations.