2. Academic Validation
  3. Astragaloside I from Astragalus Attenuates Diabetic Kidney Disease by Regulating HDAC3/Klotho/TGF- β 1 Loop

Astragaloside I from Astragalus Attenuates Diabetic Kidney Disease by Regulating HDAC3/Klotho/TGF- β 1 Loop

  • Am J Chin Med. 2024;52(6):1795-1817. doi: 10.1142/S0192415X24500708.
Xiaowei Zhang 1 2,  Jiajun Wang 1 2,  Shixie Xiang 1 2,  Liang Zhao 1 2,  Mingzhen Lv 1 2,  Yafei Duan 1 2,  Gai Gao 1 2,  Pan Wang 1 2,  Jenny Jie Chen 3,  Jiangyan Xu 1 2,  Zhishen Xie 1 2,  Zhenqiang Zhang 1 2
Affiliations

Affiliations

  • 1 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.
  • 2 Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, No. 156, Jinshui East Road, Zhengzhou, 450046, P.R. China.
  • 3 International Academic Affairs, Department Management and Science University, Persiaran Olahraga, Section 13, Shah Alam 40100, Selangor, Darul Ehsan, Malaysia.
PMID: 39347955 DOI: 10.1142/S0192415X24500708
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.

Keywords

Astragaloside I; Diabetic Kidney Disease; HDAC3; Renal Fibrosis; TGF-β1.

Figures
Products