Abstract
Gushen Jiedu capsule (GSJD) is a formula that has been widely used in traditional Chinese medicine for the prevention and treatment of diabetic nephropathy (DN). However, the mechanism underlying the protective effects of GSJD on DN is still unclear. This study was performed to clarify the therapeutic effects of GSJD on DN and its underlying mechanisms. High-fat diet- and streptozotocin-induced DN rats were treated with or without GSJD suspension by gavage for 8 weeks, and biochemical changes in blood and urine were analysed. Kidneys were isolated for histological, TUNEL and Western blot analysis. Compared to the DN group, the GSJD-treated groups exhibited decreased urinary albumin, ameliorated renal dysfunction, including serum creatinine and blood urea nitrogen, and attenuated total cholesterol, triglyceride and total protein levels. However, there were no significant effects of GSJD on body weight, fasting blood glucose or albuminuria. Histology showed that GSJD could retard the progression of DN and decrease the apoptosis rate from 52% to less than 20%. Western blot analysis showed that GSJD could regulate the mitochondrial apoptotic pathway by downregulating the expression of Bax and upregulating the expression of BCL-2 in the kidneys of DN rats. Moreover, the Akt pathway, an upstream signalling pathway of the BCL-2 family, was also ameliorated by GSJD. Further, the podocyte foot process markers podocin and nephrin were upregulated by GSJD in DN rats. This study demonstrated that GSJD might play a renoprotective role by inhibiting apoptosis and regulating the mitochondrial apoptotic and Akt pathways during pathological changes in DN.
Highlights
Diabetic nephropathy (DN) is a diabetes-induced microvascular complication that is responsible for 50% of all cases of end-stage renal disease (ESRD) and is characterized by hyperglycaemia, continuous albuminuria, high blood pressure and impaired renal function[1,2,3]
We used high-fat diet (HFD)- and STZ-induced diabetic nephropathy (DN) rats to investigate the pharmacodynamic actions of Gushen Jiedu capsule (GSJD) on DN progression and explored the mechanisms underlying the beneficial actions of GSJD in vivo
Our results demonstrated that GSJD exerted an excellent renoprotective effect on DN development, as evidenced by enhanced renal function and ameliorated renal pathological changes
Summary
Diabetic nephropathy (DN) is a diabetes-induced microvascular complication that is responsible for 50% of all cases of end-stage renal disease (ESRD) and is characterized by hyperglycaemia, continuous albuminuria, high blood pressure and impaired renal function[1,2,3]. GSJD has been used to treat early-stage DN in the clinic for over twenty years in China and was developed into a hospital preparation in recent years. It was mainly suitable for kidney yang deficiency patients[11]. The pronounced renoprotective effect of GSJD against DN prompted us to test whether GSJD attenuates DN by inhibiting apoptosis and regulating the expression of the BCL-2 family and Akt. in this study, we attempted to investigate the effects of GSJD, with a focus on its renoprotective potential and underlying anti-apoptotic mechanisms, by using a high-fat diet (HFD)- and streptozotocin (STZ)-induced animal model
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