Renoprotective Effect of the Shen-Yan-Fang-Shuai Formula by Inhibiting TNF-α/NF-κB Signaling Pathway in Diabetic Rats.

Jie Lv,Zhen Wang,Ying Wang,Jingwei Zhou,Weiwei Sun,Yaoxian Wang,Mengdi Wang,Wei Jing Liu

doi:10.1155/2017/4319057

Abstract

Diabetic kidney disease (DKD) is the leading cause of end-stage kidney disease, and satisfactory therapeutic strategies have not yet been established. The Shen-Yan-Fang-Shuai Formula (SYFSF) is a traditional Chinese formula composed of Astragali radix, Radixangelicae sinensis, Rheum officinale Baill, and four other herbs. It has been widely used as an effective treatment for DKD patients in China. However, little is known about the molecular mechanisms underlying SYFSF's renoprotection. In this study, we compared the protective effect of SYFSF to irbesartan on the histology and renal cells in type 2 DKD rat model and high-glucose (HG) cultured mesangial cells, respectively. We found that SYFSF could significantly decrease urinary albumin, cholesterol, and triglyceride. And a decrease in serum creatinine was also found in SYFSF-treated group compared with irbesartan-treated rats. In addition, SYFSF inhibited the interstitial expansion and glomerulosclerosis in diabetic rats. Notably, SYFSF markedly downregulated the expression of MCP-1, TGF-β1, collagen IV, and fibronectin in diabetic rat models and HG-induced mesangial cell models. The renoprotection was closely associated with a reduced expression of TNF-α and phosphorylated NF-κBp65. Our study suggests that SYFSF may ameliorate diabetic kidney injury. The observed renoprotection is probably attributable to an inhibition of inflammatory response and extracellular matrix (ECM) accumulation mediated by TNF-α/NF-κBp65 signaling pathway.

Highlights

Diabetic kidney disease (DKD) is one of the major microvascular complications of diabetes
The kidney weight/body weight was increased in diabetic groups (Figure 1(b)). 24-hour urinary albumin in the DKD group increased markedly which was significantly reduced in the diabetic rats treated with Shen-Yan-Fang-Shuai Formula (SYFSF) (Figure 1(c))
The serum cholesterol and triglyceride level increased in DKD compared to the control group, and SYFSF could decrease the cholesterol and triglyceride levels, while irbesartan had no effects on lipid control (Figures 1(e) and 1(f))

Summary

Introduction

Diabetic kidney disease (DKD) is one of the major microvascular complications of diabetes. It affects around 30% of diabetic patients, making it a leading cause of end-stage renal failure (ESRD) in the Western world [1]. Numerous studies have highlighted the critical role of inflammation in the pathogenesis and progression of DKD [2]. The inflammation has a strong relationship with the progression of DKD as indicated by proteinuria, GFR decline, and interstitial fibrosis [3, 4]. Many studies suggest that anti-inflammatory interventions may slow the progression of diabetic kidney disease. The medicine targeting the renin-angiotensin system (RAS) such as ACEI and ARB is the most validated clinical strategy for slowing DKD progression. The development of new therapeutic agents that prevent and effectively attenuate the DKD progression is most important

Methods

Results

Conclusion