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Jian-Pi-Yi-Shen Formula ameliorates chronic kidney disease: involvement of mitochondrial quality control network.

ABSTRACT: BACKGROUND:Jian-Pi-Yi-Shen Formula (JPYSF), a Chinese herbal decoction with the efficacies of 'fortify the spleen and tonify the kidney' and 'activate blood and resolve stasis', is effective for the treatment of chronic kidney disease in clinic. However, the underlying mechanism remains unclear. The aim of this study was to investigate the therapeutic effects and possible mechanisms of JPYSF on retarding chronic kidney disease progression in 5/6 nephrectomized (5/6 Nx) rats. METHODS:Perindopril (4?mg/kg/d) and JPYSF (2.72?g/kg/d) were administrated by gavage to 5/6 Nx rats daily for 6?weeks. The therapeutic effects of JPYSF were evaluated by renal function, pathological injury, and fibrosis. The protein levels associated with mitochondrial quality control network were measured by Western blot and immunofluorescence analysis. RESULTS:5/6 Nx rats showed obvious decline in renal function as evidenced by increased serum creatinine, blood urea nitrogen, and urinary protein excretion, and significant injury in kidney structure as evidenced by glomerular hypertrophy, tubular atrophy, and interstitial fibrosis. Administration of JPYSF for 6 weeks could improve renal function and ameliorate kidney structure injury in 5/6 Nx rats. Furthermore, the remnant kidneys of 5/6 Nx rats showed unbalanced mitochondrial quality control network manifested as decreased mitochondrial biogenesis, fusion, and mitophagy, and increased mitochondrial fission. Treatment of JPYSF could restore aforesaid aspects of mitochondrial quality control network. CONCLUSIONS:These results indicate that JPYSF can notably ameliorate 5/6 Nx-induced chronic kidney disease, which may be related with modulation of mitochondrial quality control network.

SUBMITTER: Liu X

PROVIDER: S-EPMC6302435 | biostudies-other | 2018 Dec

REPOSITORIES: biostudies-other

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Jian-Pi-Yi-Shen Formula ameliorates chronic kidney disease: involvement of mitochondrial quality control network.

Liu Xinhui X Chen Jianping J Liu Xiaoyan X Wang Dongtao D Zheng Ping P Qi Airong A Yi Tiegang T Li Shunmin S

BMC complementary and alternative medicine 20181220 1

<h4>Background</h4>Jian-Pi-Yi-Shen Formula (JPYSF), a Chinese herbal decoction with the efficacies of 'fortify the spleen and tonify the kidney' and 'activate blood and resolve stasis', is effective for the treatment of chronic kidney disease in clinic. However, the underlying mechanism remains unclear. The aim of this study was to investigate the therapeutic effects and possible mechanisms of JPYSF on retarding chronic kidney disease progression in 5/6 nephrectomized (5/6 Nx) rats.<h4>Methods</ ...[more]

PMID: 30572886

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Project description:Chronic kidney disease (CKD) is a leading public health problem with high morbidity and mortality, but the therapies remain limited. Bupi Yishen Formula (BYF) - a patent traditional Chinese medicine (TCM) formula - has been proved to be effective for CKD treatment in a high-quality clinical trial. However, BYF's underlying mechanism is unclear. Thus, we aimed to reveal BYF pharmacological mechanism against CKD by network pharmacology and experimental studies. Network pharmacology-based analysis of the drug-compound-target interaction was used to predict the potential pharmacological mechanism and biological basis of BYF. We performed a comprehensive study by detecting the expression levels of fibrotic and inflammatory markers and main molecules of candidate signal pathway in adenine-induced CKD rats and TGF-β1-induced HK-2 cells with the treatment of BYF by western blotting and RT-qPCR analyses. Using small interfering RNA, we assessed the effect of BYF on the TLR4-mediated NF-κB mechanism for CKD renal fibrosis and inflammation. Network pharmacology analysis results identified 369 common targets from BYF and CKD. Based on these common targets, the BYF intervention pathway was analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. We found that Toll-like receptor (TLR) and NF-κB signaling pathways were enriched. Then, we demonstrated that BYF significantly improved the adenine-induced CKD rat model condition by kidney dysfunction improvement and reversing renal fibrosis and inflammation. Subsequently, we investigated BYF's effect on the TLR4/NF-κB signaling pathway. We found that TLR4 and phospho-NF-κB (p-p65 and p-IKβα) expression was significantly upregulated in adenine-induced CKD rats, then partially downregulated by BYF. Furthermore, BYF inhibited fibrotic and inflammatory responses, as well as TLR4, p-p65, and p-IKβα in TGF-β1-induced HK-2 cells. Additionally, the BYF inhibitory effect on fibrosis and inflammation, and NF-κB pathway activation were significantly reduced in TGF-β1-induced HK-2 cells transfected with TLR4 siRNA. Altogether, these findings demonstrated that the suppression of TLR4-mediated NF-κB signaling was an important anti-fibrotic and anti-inflammatory mechanism for BYF against CKD. It also provided a molecular basis for new CKD treatment drug candidates.

Dataset Information

Jian-Pi-Yi-Shen Formula ameliorates chronic kidney disease: involvement of mitochondrial quality control network.

Publications

Jian-Pi-Yi-Shen Formula ameliorates chronic kidney disease: involvement of mitochondrial quality control network.

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