Trimer procyanidin oligomers contribute to the protective effects of cinnamon extracts on pancreatic β-cells in vitro

Aim: Cinnamon extracts rich in procyanidin oligomers have shown to improve pancreatic beta-cell function in diabetic db/db mice. The aim of this study was to identify the active compounds in extracts from two species of cinnamon responsible for the pancreatic beta-cell protection in vitro. Methods: Cinnamon extracts were prepared from Cinnamomum tamala (CT-E) and Cinnamomum cassia (CC-E). Six compounds procyanidin B2 (cpd1), (-)-epicatechin (cpd2), cinnamtannin B1 (cpd3), procyanidin C1 (cpd4), parameritannin A1 (cpd5) and cinnamtannin D1 (cpd6) were isolated from the extracts. INS-1 pancreatic beta-cells were exposed to palmitic acid (PA) or H2O2 to induce lipotoxicity and oxidative stress. Cell viability and apoptosis as well as ROS levels were assessed. Glucose-stimulated insulin secretion was examined in PA-treated beta-cells and murine islets. Results: CT-E, CC-E as well as the compounds, except cpd5, did not cause cytotoxicity in the beta-cells up to the maximum dosage using in this experiment. CT-E and CC-E (12.5-50 mu g/mL) dose-dependently increased cell viability in both PA- and H2O2-treated beta-cells, and decreased ROS accumulation in H2O2-treated beta-cells. CT-E caused more prominent beta-cell protection than CC-E. Furthermore, CT-E (25 and 50 mu g/mL) dose-dependently increased glucose-stimulated insulin secretion in PA-treated beta-cells and murine islets, but CC-E had little effect. Among the 6 compounds, trimer procyanidins cpd3, cpd4 and cpd6 (12.5-50 mu mol/L) dose-dependently increased the cell viability and decreased ROS accumulation in H2O2-treated beta-cells. The trimer procyanidins also increased glucose-stimulated insulin secretion in PA-treated beta-cells. Conclusion: Trimer procyanidins in the cinnamon extracts contribute to the pancreatic beta-cell protection, thus to the anti-diabetic activity.