The Herbal Formula Granule Prescription Mahuang Decoction Ameliorated Chronic Kidney Disease Which Was Associated with Restoration of Dysbiosis of Intestinal Microbiota in Rats.

Yao Ming,Chuanlan Xu,Sijing Cheng,Xiaoyu Liu,Wen Long,Junming Fan,Li Wang,Xia Zou,Sha Zhao,Hongchun Shen,Qiong Zhang,Hong-Lian Wang,Zewei Sun

doi:10.1155/2021/4602612

Abstract

Chronic kidney disease (CKD) has become a global health issue, and there is increasing evidence showing the beneficial roles of traditional Chinese medicine (TCM) in CKD treatment. Here, we studied the renoprotective role of Mahuang decoction, a famous TCM prescription, in a rat CKD model induced with the combination of doxorubicin and adenine. Our data showed that intragastric administration of Mahuang decoction inhibited the loss of bodyweight and attenuated proteinuria, serum creatinine, and blood urea nitrogen in CKD rats. Kidney histological analysis revealed decreased tubulointerstitial injury and fibrosis in CKD rats treated with Mahuang decoction accompanied with suppressed expression of TGF-β1 and phosphorylated NF-κB/P65 (p-P65) as indicated by immunohistochemistry. ELISA analysis demonstrated reduced serum levels of proinflammatory cytokines TNFα and IL-6. Most importantly, intestinal microbiota analysis by 16s rRNA-seq showed that Mahuang decoction restored the impaired richness and diversity of intestinal microflora and recovered the disrupted microbial community through reducing the abundance of deleterious microbes and promoting the expansion of beneficial microbes in CKD rats. Collectively, our findings demonstrated that Mahuang decoction mitigated kidney functional and structural impairment in CKD rats which were associated with the restoration of dysbiosis of intestinal microbiota, implying its potential in clinical CKD treatment.

Highlights

Chronic kidney disease (CKD) is characterized by long-term impairment of renal function and has become a global health issue. e incidence of CKD is estimated to be 8–16% worldwide [1]
In CKD, impaired renal function leads to increased blood urea. e diffusion of urea into the gut lumen reshapes the biochemical milieu which facilitates the propagation of urease- and uricase-containing bacteria, leading to the production of ammonia and ammonium hydroxide which damage the integrity of intestinal mucosa and enhance its permeability [3, 5]. is results in the elevated level of intestinal bacteria-originated uremic toxins in the circulation, which causes systemic inflammation as featured in CKD [5, 6]
The changed intestinal luminal milieu may facilitate the expansion of proteolytic bacteria which produce uremic toxins and suppress the growth of saccharolytic bacteria which can generate short-chain fatty acids (SCFAs), a group of metabolites beneficial to intestinal mucosal barrier integrity and enterocyte energy supply. us, this further promotes the disruption of intestinal integrity [3, 7]

Summary

Introduction

Chronic kidney disease (CKD) is characterized by long-term impairment of renal function (reduced glomerular filtration rate or increased excretion of urinary albumin or both) and has become a global health issue. e incidence of CKD is estimated to be 8–16% worldwide [1]. CKD can progress into end-stage renal disease (ESRD) associated with lethal cardiovascular complications. E dysbiosis of intestinal microbiota is associated with diverse disorders including CKD in both patient and animal models [3, 4]. In CKD, impaired renal function leads to increased blood urea. Is results in the elevated level of intestinal bacteria-originated uremic toxins in the circulation, which causes systemic inflammation as featured in CKD [5, 6]. Animal and clinical studies demonstrated that modification of intestinal microbiota through dietary intervention or supplement of prebiotics or probiotics can attenuate serum levels of uremic toxins, inflammation, and the severity of CKD [8, 9]

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Discussion

Conclusion