| Summary: | 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 <i>Rumex crispus</i> 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 IC<sub>50</sub> 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 (IC<sub>50</sub> = 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 <i>R. crispus</i> L. may be mediated by a diminished rate of disaccharide hydrolysis, associated with the inhibition of α-glucosidase. Thus, <i>R. crispus</i> L. holds promise for the development of auxiliary drugs to treat diabetes mellitus.
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