Hyperoside from Z. bungeanum leaves restores insulin secretion and mitochondrial function by regulating pancreatic cellular redox status in diabetic mice

Type 2 diabetes mellitus (T2DM) is characterized by peripheral insulin resistance and insufficient insulin secretion caused by pancreatic β-cell dysfunction. Excessive production of reactive oxygen species (ROS) and activation of caspases in mitochondria inhibit insulin secretion and promote apoptosis of pancreatic β-cells. Studies have demonstrated that positive correlation between the consumption of flavonoid-rich diets and diabetes prevention. Zanthoxylum bungeanum leaves have been used as food for a long time and are rich in flavonoids with strong radical scavenging abilities. We and others have identified hyperoside as the major bioactive component of total flavonoids exacted from Zanthoxylum bungeanum leaves. We hypothesize that hyperoside from Z. bungeanum leaves (HZL) may prevent T2DM by inhibiting excessive ROS formation and reducing pancreatic β-cells apoptosis. In current study, HZL was administered to high fat diet and alloxan-induced diabetic mice, and appeared to significantly ameliorate the damage of glucose metabolism and insulin secretion as well as restore the structural integrity of pancreas, and inhibit β-cell apoptosis. Pancreatic antioxidant enzyme activities were also restored by HZL supplementation. In cultured MIN6 cells, which produce and secret insulin, HZL treatment restored insulin secretion through inhibiting the expression of TXNIP and lowering intracellular calcium concentration. These observations mechanistically linked the beneficial effects of HZL with the regulation on cellular redox status and mitochondrial function. Taken together, our findings suggest that HZL has protective effect on pancreatic β-cell function and may be a beneficial nutritional supplementation for prevention and adjuvant therapy of T2DM.