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Journal of Translational Medicine
Published in: Journal of Translational Medicine 1/2024

Open Access 01-12-2024 | Ulcerative Colitis | Research

Blockade of PI3K/AKT signaling pathway by Astragaloside IV attenuates ulcerative colitis via improving the intestinal epithelial barrier

Authors: Xinhui Zhang, Fan Zhang, Yan Li, Na Fan, Ke Zhao, Anding Zhang, Jiefang Kang, Yan Lin, Xiaochang Xue, Xun Jiang

Published in: Journal of Translational Medicine | Issue 1/2024

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Abstract

Background

The specific pathogenesis of UC is still unclear, but it has been clear that defects in intestinal barrier function play an important role in it. There is a temporary lack of specific drugs for clinical treatment. Astragaloside IV (AS-IV) is one of the main active ingredients extracted from Astragalus root and is a common Chinese herbal medicine for the treatment of gastrointestinal diseases. This study aimed to determine whether AS-IV has therapeutic value for DSS or LPS-induced intestinal epithelial barrier dysfunction in vivo and in vitro and its potential molecular mechanisms.

Methods

The intestinal tissues from UC patients and colitis mice were collected, intestinal inflammation was observed by colonoscopy, and mucosal barrier function was measured by immunofluorescence staining. PI3K/AKT signaling pathway activator YS-49 and inhibitor LY-29 were administered to colitic mice to uncover the effect of this pathway on gut mucosal barrier modulation. Then, network pharmacology was used to screen Astragaloside IV (AS-IV), a core active component of the traditional Chinese medicine Astragalus membranaceus. The potential of AS-IV for intestinal barrier function repairment and UC treatment through blockade of the PI3K/AKT pathway was further confirmed by histopathological staining, FITC-dextran, transmission electron microscopy, ELISA, immunofluorescence, qRT-PCR, and western blotting. Finally, 16 S rRNA sequencing was performed to uncover whether AS-IV can ameliorate UC by regulating gut microbiota homeostasis.

Results

Mucosal barrier function was significantly damaged in UC patients and murine colitis, and the activated PI3K/AKT signaling pathway was extensively involved. Both in vivo and vitro showed that the AS-IV-treated group significantly relieved inflammation and improved intestinal epithelial permeability by inhibiting the activation of the PI3K/AKT signaling pathway. In addition, microbiome data found that gut microbiota participates in AS-IV–mediated intestinal barrier recovery as well.

Conclusions

Our study highlights that AS-IV exerts a protective effect on the integrality of the mucosal barrier in UC based on the PI3K/AKT pathway, and AS-IV may serve as a novel AKT inhibitor to provide a potential therapy for UC.

Graphical abstract

Appendix
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Metadata
Title
Blockade of PI3K/AKT signaling pathway by Astragaloside IV attenuates ulcerative colitis via improving the intestinal epithelial barrier
Authors
Xinhui Zhang
Fan Zhang
Yan Li
Na Fan
Ke Zhao
Anding Zhang
Jiefang Kang
Yan Lin
Xiaochang Xue
Xun Jiang
Publication date
01-12-2024
Publisher
BioMed Central
Published in
Journal of Translational Medicine / Issue 1/2024
Electronic ISSN: 1479-5876
DOI
https://doi.org/10.1186/s12967-024-05168-w

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