Renoprotective effects of Gushen Jiedu capsule on diabetic nephropathy in rats

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. 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 1-3. Additionally, DN is a major risk factor for mortality in patients with diabetic complications worldwide 4,5. Hence, the prevention and treatment of DN have become a serious health issue, and the development of DN medications would be beneficial. Traditional Chinese medicine (TCM) has been used in the treatment of diabetes and related complications for thousands of years in China, which emphasizes the whole regulatory action on the human body 6,7. Thus, TCM formulae have become an important source for the discovery of new medications to prevent and treat DN 8,9. For instance, the NaoXinTong capsule 10 improves glomerular function, inhibits extracellular matrix accumulation, activates the insulin signalling pathway and improves glucose metabolism in db/db mice, suggesting a favourable effect on kidney function. The Gushen Jiedu capsule (GSJD) originated from the classic kidney-tonifying prescription of "Shuilu Erxian Dan" in the Song Dynasty (1170 AD) in China (Supplementary Fig. S1), containing Semen Euryales, Fructus Rosa laevigata, Rhizome Coptis chinensis, Rhizome Rheum tanguticum, Radix Astragalus membranaceus and ...

Repurposing a clinically approved prescription Colquhounia root tablet to treat diabetic kidney disease via suppressing PI3K/AKT/NF-kB activation

“…According to the United States Renal Data System, DKD accounts for up to 50% of end-stage renal disease (ESRD) cases [ 1 , 2 ], and also the main risk factor for death of patients with diabetes [ 3 , 4 ]. It is characterized by hyperglycemia, persistent proteinuria, hypertension and impaired renal function [ 5 – 8 ]. The main therapeutic strategy of the early DKD is hypoglycemic and antihypertensive combined symptomatic treatment, and the main therapeutic strategy of the late DKD is kidney transplantation.…”

Tiliacora triandra extract and its major constituent attenuates diabetic kidney and testicular impairment by modulating redox imbalance and pro‐inflammatory responses in rats

“…Although, testicular dysfunction in diabetes is not life threatening, the psychological and emotional problems associated with it is huge. Whereas, complications of the kidney arising from diabetes can be fatal and can result in end stage kidney disease, kidney failure or even death 9 . The etiology of diabetes induced kidney and testes damage is assumed to be multifarious and complicated, however, oxidative stress and excessive accumulation of reactive oxygen species (ROS) due to chronic hyperglycaemia has been partly or wholly implicated in the onset and progression of these damages 10–13 .…”

“…Whereas, complications of the kidney arising from diabetes can be fatal and can result in end stage kidney disease, kidney failure or even death. 9 The etiology of diabetes induced kidney and testes damage is assumed to be multifarious and complicated, however, oxidative stress and excessive accumulation of reactive oxygen species (ROS) due to chronic hyperglycaemia has been partly or wholly implicated in the onset and progression of these damages. [10][11][12][13] Hyperglycaemia activates signalling pathways that enhances the accumulation of ROS and oxidative stress which in turn leads to the formation of advanced glycation end products, pro-inflammatory mediators and apoptosis which play a critical role in diabetic complications including kidney and testes damage.…”

Comparison of efficacy and safety of traditional Chinese patent medicines for diabetic nephropathy

“…Shenshuaining capsules [ 22 ] can significantly reduce serum urea nitrogen and creatinine and improve renal function. Gushen Jiedu capsules [ 23 ] can inhibit apoptosis and protect the kidney in rats with DN. Yishen capsules [ 24 ] promote podocyte autophagy and improve DN by regulating the SIRT1/NF-kappaB signaling pathway.…”