Evaluation of the potential hypoglycemic and beta-cell protective constituents isolated from corni fructus to tackle insulin-dependent diabetes mellitus

Corni fructus is the fruit of Cornus officinalis Sieb. et Zucc. and has attracted much interest due to its traditional applications and active fraction that reportedly possesses antidiabetic effects. In this study, we isolated 12 compounds from Corni fructus including three flavonoids, two iridoid glycosides, three phenolic compounds, and two triterpenoids, together with cornuside (11) and 2-butoxybutanedioic acid (12). Chemical structures were identified by ¹H, ¹³C NMR, DEPT, COSY, HSQC, and HMBC spectral analyses. Furthermore, the glucose uptake efficiency, messenger (m)RNA expression of phosphoenolpyruvate carboxykinase (PEPCK), and prevention of cytokine-mediated cytotoxicity in the presence of test agents were evaluated. While CH and CB significantly increased glucose uptake from muscle, compounds 3 and 8, each at 50 μM, significantly suppressed PEPCK mRNA expression. Finally, compound 5, at 50 and 100 μM, effectively attenuated β-cell death. In conclusion, those compounds could contribute to the antihyperglycemic and β-cell-protective actions of Corni fructus against diabetes mellitus.