黄芪中的黄芪皂苷 I 通过调节 HDAC3/Klotho/TGF-β1 环路减轻糖尿病肾病的病情

The American journal of Chinese medicine Pub Date : 2024-01-01 Epub Date: 2024-09-30 DOI:10.1142/S0192415X24500708
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
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引用次数: 0

摘要

糖尿病肾病(DKD)已成为终末期肾病(ESRD)的主要病因,因此迫切需要针对糖尿病肾病的预防策略。黄芪皂苷 I(ASI)是从黄芪中提取的一种生物活性皂苷,已被证实具有多种生物活性。本研究利用体内 db/db 小鼠和体外高糖(HG)诱导的 SV40-MES-13 细胞研究 ASI 对 DKD 的治疗潜力及其分子机制。结果表明,ASI能明显改善db/db小鼠的肾功能障碍,减轻肾组织的病理改变。此外,在 db/db 小鼠和 HG 诱导的 SV40-MES-13 细胞中,ASI 都能降低肾纤维化制造者的水平,并抑制 TGF-[式中:见正文]1/Smad2/3 通路的激活。此外,ASI 还能下调 HDAC3 的表达,上调 Klotho 的表达,并增强 Klotho 的释放。ASI直接与HDAC3结合,HDAC3激动剂ITSA-1逆转了ASI对Klotho/TGF-[式中:见正文]1/Smad2/3介导的DKD肾纤维化的有益影响。总之,ASI能减轻DKD的肾纤维化,可能是通过同时抑制HDAC3和TGF-[式:见正文]1,从而调节HDAC3介导的Klotho/TGF-[式:见正文]1/Smad2/3通路。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Astragaloside I from Astragalus Attenuates Diabetic Kidney Disease by Regulating HDAC3/Klotho/TGF-β1 Loop.

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.

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