Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Trifolirhizin relieves renal injury in a diabetic nephropathy model by inducing autophagy and inhibiting oxidative stress through the regulation of PI3K/AKT/mTOR pathway

Yunyi Xin¹, Xiao Xu¹ , Xufeng Yang¹, Yufan Chen², Danning Zhu³

¹Department of Gerontology, Suzhou Ninth Peopleâ€™s Hospital, Suzhou City, Jiangsu Province 215299, China; ²Department of General Surgery, The Affiliated Jiangsu Shengze Hospital of Nanjing Medical University, Suzhou City, Jiangsu Province 215299, China; ³Department of Dermatology, The Affiliated Wuxi No. 2 Peopleâ€™s Hospital of Nanjing Medical University, Wuxi City, Jiangsu Province 214000, China.

For correspondence:- Xiao Xu Email: xiao_xu0428@163.com Tel:+8651282881190

Accepted: 26 September 2022 Published: 28 October 2022

Citation: Xin Y, Xu X, Yang X, Chen Y, Zhu D. Trifolirhizin relieves renal injury in a diabetic nephropathy model by inducing autophagy and inhibiting oxidative stress through the regulation of PI3K/AKT/mTOR pathway. Trop J Pharm Res 2022; 21(10):2107-2113 doi: 10.4314/tjpr.v21i10.10

© 2022 The authors.
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Abstract

Purpose: To evaluate the effects of trifolirhizin on diabetic nephropathy (DN), and the mechanism of action.

Methods: Male db/db mice (8 weeks, n = 24) and age-matched control mice (n = 6) were obtained. The mice were further divided into four groups and administered increasing doses of trifolirhizin (0, 12.5, 25 and 50 mg/kg). Histological analysis of renal tissues were performed by H & E staining. Blood urea nitrogen (BUN) and creatinine were determined using enzyme-linked immunosorbent assay (ELISA). Immunoblot and TUNEL assay were performed to investigate the effect of trifolirhizin on autophagy and apoptosis, while ELISA and dihydroethidium (DHE) staining were conducted to evaluate reactive oxygen species (ROS), malondialdehyde (MDA) and superoxide dismutase (SOD) levels. The effect of trifolirhizin on PI3K/AKT/mTOR pathway was determined using Immunoblot assays.

Results: Trifolirhizin alleviated renal injury in diabetic mice, and also activate autophagy and inhibited apoptosis in the renal tissues in diabetic mice (p < 0.001). In addition, trifolirhizin inhibited the oxidative stress response in the renal tissue in diabetic mice (p < 0.001). Trifolirhizin further inhibited PI3K/AKT/mTOR pathway and therefore relieved renal injury in the diabetic nephropathy model (p < 0.001).

Conclusion: Trifolirhizin alleviates renal injury in diabetic mice, activates autophagy, and inhibits apoptosis in renal tissue of diabetic mice. Therefore, trifolirhizin is a promising a promising drug for the treatment of DN.

Keywords: Diabetic nephropathy, Trifolirhizin, Autophagy, Oxidative stress, PI3K/AKT/mTOR pathway