Xiaowei Zhang, Jiajun Wang, Shixie Xiang, Liang Zhao, Mingzhen Lv, Yafei Duan, Gai Gao, Pan Wang, Jenny Jie Chen, Jiangyan Xu, Zhishen Xie, Zhenqiang Zhang
{"title":"Astragaloside I from <i>Astragalus</i> Attenuates Diabetic Kidney Disease by Regulating HDAC3/Klotho/TGF-<b>β</b>1 Loop.","authors":"Xiaowei Zhang, Jiajun Wang, Shixie Xiang, Liang Zhao, Mingzhen Lv, Yafei Duan, Gai Gao, Pan Wang, Jenny Jie Chen, Jiangyan Xu, Zhishen Xie, Zhenqiang Zhang","doi":"10.1142/S0192415X24500708","DOIUrl":null,"url":null,"abstract":"<p><p>Diabetic kidney disease (DKD) has become the primary cause of end-stage renal disease (ESRD), causing an urgent need for preventive strategies for DKD. Astragaloside I (ASI), a bioactive saponin extracted from <i>Astragalus membranaceus</i> (Fisch.) Bunge has been demonstrated to possess a variety of biological activities. This study investigates the therapeutic potential of ASI in DKD and the underlying molecular mechanism using <i>db/db</i> mice <i>in vivo</i> and high glucose (HG)-induced SV40-MES-13 cells <i>in vitro</i>. The results indicated that ASI significantly ameliorated renal dysfunction and mitigated the pathological alterations in the renal tissues of <i>db/db</i> mice. Moreover, ASI was found to reduce the levels of renal fibrosis makers and suppress the activation of TGF-β1/Smad2/3 pathway in both <i>db/db</i> mice and HG-induced SV40-MES-13 cells. Furthermore, ASI downregulated HDAC3 expression, upregulated Klotho expression, and enhanced Klotho release. ASI is directly bound to HDAC3, and the beneficial effects of ASI on Klotho/TGF-β1/Smad2/3-mediciated renal fibrosis in DKD were reversed by the HDAC3 agonist ITSA-1. In conclusion, ASI attenuates renal fibrosis in DKD, and may act through concurrently inhibiting HDAC3 and TGF-β1, thereby regulating HDAC3-mediciated Klotho/TGF-β1/Smad2/3 pathway.</p>","PeriodicalId":94221,"journal":{"name":"The American journal of Chinese medicine","volume":" ","pages":"1795-1817"},"PeriodicalIF":0.0000,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"The American journal of Chinese medicine","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1142/S0192415X24500708","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/9/30 0:00:00","PubModel":"Epub","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
Abstract
Diabetic kidney disease (DKD) has become the primary cause of end-stage renal disease (ESRD), causing an urgent need for preventive strategies for DKD. Astragaloside I (ASI), a bioactive saponin extracted from Astragalus membranaceus (Fisch.) Bunge has been demonstrated to possess a variety of biological activities. This study investigates the therapeutic potential of ASI in DKD and the underlying molecular mechanism using db/db mice in vivo and high glucose (HG)-induced SV40-MES-13 cells in vitro. The results indicated that ASI significantly ameliorated renal dysfunction and mitigated the pathological alterations in the renal tissues of db/db mice. Moreover, ASI was found to reduce the levels of renal fibrosis makers and suppress the activation of TGF-β1/Smad2/3 pathway in both db/db mice and HG-induced SV40-MES-13 cells. Furthermore, ASI downregulated HDAC3 expression, upregulated Klotho expression, and enhanced Klotho release. ASI is directly bound to HDAC3, and the beneficial effects of ASI on Klotho/TGF-β1/Smad2/3-mediciated renal fibrosis in DKD were reversed by the HDAC3 agonist ITSA-1. In conclusion, ASI attenuates renal fibrosis in DKD, and may act through concurrently inhibiting HDAC3 and TGF-β1, thereby regulating HDAC3-mediciated Klotho/TGF-β1/Smad2/3 pathway.