Huangqi-Danshen Decoction Ameliorates Adenine-Induced Chronic Kidney Disease by Modulating Mitochondrial Dynamics.

Xinhui Liu,Shiying Huang,Lin Zheng,Fochang Wang,Jianping Chen,Jiandong Lu,Shunmin Li

doi:10.1155/2019/9574045

Abstract

Chronic kidney disease (CKD) is a leading public health problem with high morbidity and mortality. However, the therapies remain limited. Traditional Chinese medicine (TCM) has been used for treating kidney disease for thousands of years and is an effective alternative treatment for CKD patients in China and other Asian countries. In the present study, we aimed to investigate the effect and mechanism of Huangqi-Danshen decoction (HDD), a TCM herbal decoction, on treating CKD. CKD rat model was induced by adding 0.75% adenine to the diet for 4 weeks. HDD extract was administrated orally to CKD rats at the dose of 4.7 g/kg/d for consecutive 4 weeks in adenine-induced CKD rats. Kidney function was evaluated by the levels of serum creatinine (Scr) and blood urea nitrogen (BUN). The pathological changes of kidney tissues were observed by periodic acid-Schiff (PAS) and Masson's trichrome staining. The proteins expression of renal fibrosis and mitochondrial dynamics were determined and quantified by Western blot analysis. CKD rats showed obvious decline in renal function as evidenced by increased levels of Scr and BUN, which were blunted by HDD treatment. HDD could also improve tubular atrophy and interstitial fibrosis of CKD rats. Moreover, HDD downregulated fibronectin, type IV collagen, and α-smooth muscle actin expression in CKD rats. Furthermore, mitochondrial dynamics was disturbed in CKD rats, which manifested as increased mitochondrial fission and decreased mitochondrial fusion. HDD treatment restored mitochondrial dynamics in CKD rats by repressing dynamin-related protein 1 and Mid 49/51 expression, promoting mitofusin 2 expression, and suppressing optic atrophy 1 proteolysis. In conclusion, HDD could significantly retard CKD progression through modulating mitochondrial dynamics.

Highlights

Chronic kidney disease (CKD) is defined as abnormalities of kidney structure or function persisting for at least 3 months, regardless of the underlying cause [1]
Huangqi-Danshen decoction (HDD) had no effect on liver function as estimated by the levels of aspartate transaminase (AST) and alanine transaminase (ALT), which means the treatment dosage of HDD in current study is safe (Supplementary Table 1)
These data indicated that CKD model was established successfully, and HDD prevented renal function decline in CKD rats

Summary

Introduction

Chronic kidney disease (CKD) is defined as abnormalities of kidney structure or function persisting for at least 3 months, regardless of the underlying cause [1]. The prevalence of all stages of CKD varies between 7 and 12% in the different regions of the world [1]. The mainstay therapeutic approach to retard progressive CKD or renal fibrosis is based on renninangiotensin system (RAS) blockade as well as blood pressure and glycemic control [3,4,5]. These interventions could not prevent the progression to end-stage renal disease (ESRD). The benefit of standard therapies varies across stages of CKD [6]. Mechanism investigation, discovering therapeutic targets, and searching effective medications are always necessary for CKD treatment

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