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

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.

Effect of Jiawei Tangzhiqing granules on JAK2/STAT3 signal pathway and Th17/Treg ratio in diabetic nephropathy mice

“…Conversely, the mice receiving a high dose of Traditional Chinese Medicine demonstrated an upturn in body mass coupled with a decline in both 24-h urine production and their intake of feed and water when measured against model group. In addition, the levels of FBG, HbA1c, CHOl, LDL, CREA, BUN, mALB and 24 h UTP were decreased significantly, indicating that the modified sugar-and fat-clearing granules mitigated disorders in glucose and lipid metabolism, protected kidney function, and reduced proteinuria [10]. Results from histology suggest that at high-dose, the granules significantly reduced DN-induced pathological changes, and alleviated DN-mediated cell dysfunction and structural damage such as glomerular basement membrane thickening and renal tissue fibrosis [11].…”