In vitro anti-diabetic activities of phytochemicals isolated from Cornus officinalis fruits

Four previously undescribed compounds, including two dihydroisocoumarin glycosides (1 and 2), a truxillic acid derivative (4), and a cadinane-type sesquiterpene (5), were isolated from the fruits of Cornus officinalis Sieb. et Zucc., along with seven known ones (3, 6-11). Their chemical structures were determined by extensive spectroscopic methods and computational analyses. All isolated compounds were evaluated for the effects on glucose consumption in insulin-resistant (IR) HepG2 cells. The compounds exhibited no significant cytotoxicity at 10.0 μM in the CCK-8 assay. Compounds 2, 3, and 8 significantly increased glucose consumption (P < 0.05) at 5.0 and 10.0 μM. The 2-NBDG labeling indicated that compounds 2 and 8 significantly increased glucose uptake at 10 μM. Moreover, compounds 2 and 8 also significantly increased insulin receptor (INSR) expression, indicating their potential to upregulate the INSR in the cytomembrane and enhance glucose uptake.