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

Abstract

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.Conclusions: 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.

The combination of endurance exercise and SGTC (Salvia–Ginseng–Trigonella–Cinnamon) ameliorate mitochondrial markers’ overexpression with sufficient ATP production in the skeletal muscle of mice fed AGEs-rich high-fat diet

“…This is because the energy required by diabetic cells is less than β-oxidation rate [ 22 ]. We speculated that most of the electron energy in ETC would be consumed for the sake of ROS production, as we observed in our previous study [ 16 ]. However, this need to be carefully elucidated in further studies.…”

“…Some studies have shown an increase in Ucp3 expression after ingestion of Salvia and Ginseng extract (two components of SGTC) and Metformin [ 34 – 36 ]. Additionally, SGTC and Met antioxidant capacity might also improve the functional role of mitochondria by ROS reduction according to our previous study (Additional file 1 : Figure S2) [ 13 , 16 , 37 , 38 ].…”

“…Nevertheless, many studies have demonstrated the antioxidant properties of each component of the drug [ 13 , 38 ]. Endurance exercise enhances the mitochondrial function and ATP production through Ppargc1α and Tfam pathways whereas SGTC may act by ameliorating the expression of mitochondrial markers and its antioxidant properties [ 16 ]. It is likely that the herbal component in Ex + SGTC group, decreased the rate of ROS and significantly improved the rate of ATP production and mitochondrial overall functionality compared to the Ex group (Fig.…”

“…The aqueous extract of the four herbs was provided as previously described [ 16 ]. The final extract was consisted of 50% (w/v) of Salvia officinalis , 21% (w/v) of Panax ginseng , 21% (w/v) of Trigonella foenum-greacum , and 8% (w/v) of Cinnamomum zeylanicum .…”

Metformin attenuates H2O2‑induced osteoblast apoptosis by regulating SIRT3 via the PI3K/AKT pathway

“…The use of metformin in postmenopausal osteoporosis has not yet been investigated. Since metformin is able to improve the oxidative state in numerous diseases, including diabetes and fatty liver (11,12), the aim of the present study was to determine the role of metformin in the treatment of postmenopausal osteoporosis.…”