1. Astragaloside I from <italic>Astragalus</italic> Attenuates Diabetic Kidney Disease by Regulating HDAC3/Klotho/TGF-<bold>β</bold>1 Loop.
- Author
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Zhang, Xiaowei, Wang, Jiajun, Xiang, Shixie, Zhao, Liang, Lv, Mingzhen, Duan, Yafei, Gao, Gai, Wang, Pan, Jie Chen, Jenny, Xu, Jiangyan, Xie, Zhishen, and Zhang, Zhenqiang
- 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 usingdb/db micein vivo and high glucose (HG)-induced SV40-MES-13 cellsin vitro . The results indicated that ASI significantly ameliorated renal dysfunction and mitigated the pathological alterations in the renal tissues ofdb/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 bothdb/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. [ABSTRACT FROM AUTHOR]- Published
- 2024
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