AUTHOR=Tan Zhuojing , Si Yachen , Yu Yan , Ding Jiarong , Huang Linxi , Xu Ying , Zhang Hongxia , Lu Yihan , Wang Chao , Yu Bing , Yuan Li 

TITLE=Yi-Shen-Hua-Shi Granule Alleviates Adriamycin-Induced Glomerular Fibrosis by Suppressing the BMP2/Smad Signaling Pathway

JOURNAL=Frontiers in Pharmacology

VOLUME=Volume 13 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2022.917428

DOI=10.3389/fphar.2022.917428

ISSN=1663-9812

ABSTRACT=Focal segmental glomerulosclerosis (FSGS) is a common clinical condition with manifestations of nephrotic syndrome and fibrosis of the glomeruli and interstitium. Yi-Shen-Hua-Shi (YSHS) granule has been shown to have a good effect in alleviating nephrotic syndrome (NS) in the clinic and in animal models of FSGS, but whether it can alleviate renal fibrosis in FSGS, and its mechanism and targets are not clear. In this study, we explored the anti-fibrotic effect and the targets of YSHS granule in Adriamycin (ADR)-induced FSGS model, and found that YSHS granule significantly improved the renal function of ADR-induced FSGS model mice and also significantly reduced the deposition of collagen fibers and the expression of mesenchymal cell markers FN, Vimentin and α-SMA in the glomeruli of ADR-induced FSGS mice, suggesting that YSHS granule inhibited the fibrosis of sclerotic glomeruli. Subsequently, network pharmacology-based approach was used to identify the potential targets of YSHS granule for the alleviation of glomerulosclerosis in FSGS and the results showed that YSHS granule down-regulated the expression of BMP2, GSTA1, GATS3, BST1, and S100A9 and up-regulated the expression of TTR and GATM in ADR-induced FSGS model mice. We also proved that YSHS granule inhibited the fibrosis in the glomeruli of ADR-induced FSGS model mice through the suppressing of BMP2/Smad signaling pathway.