A combination of herbal compound (SPTC) along with exercise or metformin more efficiently alleviated diabetic complications through down-regulation of stress oxidative pathway upon activating Nrf2-Keap1 axis in AGE rich diet-induced type 2 diabetic mice

BACKGROUND: SPTC is a mix of four herbal components (Salvia officinalis, Panax ginseng, Trigonella foenum-graeceum, and Cinnamomum zeylanicum) which might be prevented the development of AGE rich diet-induced diabetic complication and liver injury through activated the nuclear factor erythroid-2-related-factor-2 (Nrf2) pathway. Nrf2, as a master regulator of antioxidant response elements by activating cytoprotective genes expression, is decreased oxidative stress that associated with hyperglycemia and increases insulin sensitivity. the aim of this study was to assess whether the combination therapy of SPTC along with exercise or metformin moderate oxidative stress related liver injurie with more favorable effects in the treatment of AGE rich diet-induced type 2 diabetic mice. METHODS: We induced diabetes in C57BL/6 mice by AGE using a diet supplementation and limitation of physical activity. After 16 weeks of intervention, AGE fed mice were compared to control mice. Diabetic mice were assigned into seven experimental groups (each group; n = 5): diabetic mice, diabetic mice treated with SPTC (130 mg/kg), diabetic mice treated with Salvia Officinalis (65 mg/kg), diabetic mice treated with metformin (300 mg/kg), diabetic mice with endurance exercise training, diabetic mice treated with SPTC + metformin (130/300 mg/kg), diabetic mice treated with SPTC + exercise training. RESULTS: SPTC + exercise and SPTC + metformin reduced diabetic complications like gain weight, water and calorie intake, blood glucose, insulin, and GLUT4 content more efficiently than each treatment. These combinations improved oxidative stress hemostasis by activating the Nrf2 signaling pathway and attenuating keap1 protein more significantly. CONCLUSION: Eventually, combined treatment of SPTC with exercise or metformin as a novel approach had more beneficial effects to prevent the development of diabetes and oxidative stress associated with hyperglycemia. [Image: see text]