Calein C, an Alpha-Glucosidase Inhibitor from Brickellia cavanillesii

An aqueous extract from the aerial parts of Brickellia cavanillesii (Asteraceae), orally administered into different groups of normal and streptozotocin (STZ)-induced diabetic mice (100mg/kg) showed significant hypoglycemic and antihyperglycemic effects. The antihyperglycemic effect was assessed by means of oral glucose and sucrose tolerance tests (OGT and OST). In particular, the infusion at the dose of 316mg/kg decreased blood glucose levels in STZ-diabetic mice after an oral sucrose load suggesting that its antihyperglycemic effect is due to an inhibition of alpha-glucosidase at the intestinal level. An in vitro assay confirmed this hypothesis. From the active extract caleins C (1) and B (2), quercetin and desmethylisoencecalin were isolated from the active fractions. When tested in vitro, only compounds 1 and 2 inhibited the activity of yeast-alpha-glucosidase being 1 (IC₅₀=0.11779 mM) the most active. Docking analysis predicted that 1 binds to the enzyme in the same pocket of acarbose, a potent inhibitor of intestinal alpha-glucosidases used as a positive control. The present study provides scientific support of the use of B. cavanillesii in Mexican folk medicine for the treatment of diabetes.

Acknowledgements: This work was supported by grants from DGAPA (IN218110) and CONACyT (150966 and 99395).