Enhanced Hypoglycemic Bioactivity via RAS/Raf‐1/MEK/ERK Signaling Pathway by Combining Capsaicin and QUERCETIN from Chili Peppers

Scope This research work is designed and conducted to explore the joint effect of capsaicin and quercetin and the potential mechanism for the regulation of hyperglycemia. Methods and results Insulin‐resistance HepG2 cell model and high‐fat diet combined with streptozotocin‐induced type 2 diabetes mouse model are applied for the investigation. The results illustrate that capsaicin and quercetin can exert hypoglycemic effects via reducing the concentrations of serum lipids of total cholesterol, triglyceride and low‐density lipoprotein cholesterol, decreasing hepatic enzyme activities of phosphoenolpyruvate, carboxykinase, and glucose‐6‐phosphatase, as well as improving the histopathological morphology of liver and pancreas tissues. After administration with capsaicin and quercetin, the relative protein expression abundance of Ras, Raf‐1, MEK1/2, and ERK1/2 is obviously attenuated compared to diabetic mice. Capsaicin and quercetin at a ratio of 3:1 are generally determined as the optimal combination. Conclusion Capsaicin and quercetin present in the chili pepper fruit can act in a synergistic way to alleviate hyperglycemia. This study provides supporting data for the discovery of novel anti‐diabetic components and for the valorization of chili pepper industry.