Astragaloside IV attenuates high-glucose-Induced peritoneal fibrosis via modulation of the ENKUR/PI3K/Akt signalling pathway

Tianxin Jiang, Lijie Zhang, Jiahan Liu, Xinxin Xu, Yuanyuan Shi, Zhanzheng Zhao and Jing Xiao

PLOS ONE, 2026, vol. 21, issue 5, 1-13

Abstract: This study aimed to explore the mechanisms by which Astragaloside IV (AS-IV), a major bioactive component of Astragalus membranaceus, mitigates high-glucose-induced peritoneal fibrosis (PF) in peritoneal dialysis (PD). Using both in vivo (uremic rat model) and in vitro (human peritoneal mesothelial cells) approaches, we observed that AS-IV treatment was associated with a significant attenuation of PF. This effect was mediated through the inhibition of epithelial-mesenchymal transition (EMT) and fibrosis. In vivo, AS-IV reduced extracellular matrix deposition and collagen accumulation, downregulated EMT and fibrosis markers (α-SMA, collagen IV), and restored E-cadherin levels. Notably, these changes correlated with the downregulation of ENKUR, pPI3K, and pAkt. The in vitro results corroborated these findings, showing that AS-IV suppressed EMT without cytotoxic effects. Our data indicate that AS-IV may exert antifibrotic effects via modulation of the ENKUR/PI3K/Akt signaling pathway, suggesting a potential target for the prevention of PF.

Date: 2026
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Persistent link: https://EconPapers.repec.org/RePEc:plo:pone00:0348762

DOI: 10.1371/journal.pone.0348762

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