• Xiaowei Zhang, Jiajun Wang, Shixie Xiang, Liang Zhao, Mingzhen Lv, Yafei Duan, Gai Gao, Pan Wang, Jie ChenJennyJ0009-0000-6769-7947International Academic Affairs, Department Management and Science University, Persiaran Olahraga, Section 13, Shah Alam 40100, Selangor, Darul Ehsan, Malaysia., Jiangyan Xu, Zhishen Xie, and Zhenqiang Zhang.
• Henan Collaborative Innovation Center for Research and Development on the Whole Industry, Chain of Yu-Yao, Henan University of Chinese Medicine, No. 156, Jinshui East Road, Zhengzhou, 450046, P.R. China.
• Am. J. Chin. Med. 2024 Jan 1; 52 (6): 179518171795-1817.

AbstractDiabetic 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.

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