Abstract
BackgroundDiabetic nephropathy serves as one of the most regular microvascular complications of diabetes mellitus and is the main factor that causes end-stage renal disease and incident mortality. As the beneficial effect and minute adverse influence of Celastrol on the renal system requires further elucidation, the renoprotective function of Celastrol in early diabetic nephropathy was investigated.MethodsIn high-fat and high-glucose diet/streptozotocin-induced diabetic rats which is the early diabetic nephropathy model, ALT, AST, 24 h urinary protein, blood urea nitrogen, and serum creatinine content were observed. Periodic acid-Schiff staining, enzyme-linked immunosorbent assay, immunohistochemical analysis, reverse transcription-polymerase chain reaction, and western blot analysis were used to explore the renoprotective effect of Celastrol to diabetic nephropathy rats and the underlying mechanism.ResultsHigh dose of Celastrol (1.5 mg/kg/d) not only improved the kidney function of diabetic nephropathy (DN) rats, and decreased the blood glucose and 24 h urinary albumin, but also increased the expression of LC3II and nephrin, and downregulated the expression of PI3K, p-AKT, and the mRNA level of NF-κB and mTOR.ConclusionCelastrol functions as a potential therapeutic substance, acting via the PI3K/AKT pathway to attenuate renal injury, inhibit glomerular basement membrane thickening, and achieve podocyte homeostasis in diabetic nephropathy.
Highlights
Diabetic nephropathy serves as one of the most regular microvascular complications of diabetes mellitus and is the main factor that causes end-stage renal disease and incident mortality
The body weight was significantly increased compared to the Diabetic nephropathy (DN) group (p < 0.05), while 24 h urinary volume in DN + CH group and blood glucose in the DN + CH and DN + INH groups were significantly decreased compared to DN group (p < 0.05)
These results demonstrated that Celastrol treatment could ameliorate weight, 24 h urinary volume and glucose in rats with early DN
Summary
Diabetic nephropathy serves as one of the most regular microvascular complications of diabetes mellitus and is the main factor that causes end-stage renal disease and incident mortality. Diabetic nephropathy (DN), a common microvascular change of diabetes mellitus (DM), is the main cause of end-stage renal disease (ESRD) [1]. Macrophage-regulated inflammation plays a role in progression of DN [6] and suppressing NF-κB signal could ameliorate DN [7, 8]. Experimental data showed that PI3K/AKT pathway plays a crucial role in boosting epithelial-mesenchymal transition [10] and blocking autophagy with the downstream signal mTOR [11]. MTOR blockade exerts a beneficial effect in DN, suggesting that the mTOR pathway plays an important pathogenic role in DN [14, 15]. PI3K/AKT, mTOR, and NF-κB are possible mediators of DN progression
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