Astragalus membranaceus extract attenuates ulcerative colitis by integrating multiomics and the PI3K/AKT signaling pathway

IntroductionUlcerative colitis (UC) is a chronic, non-specific inflammatory bowel disease (IBD) that severely impairs the quality of life of affected individuals. Astragalus membranaceus (Fisch.) Bge. [Fabaceae; Astragali radix] (AM), a widely used Chinese medicine, has active ingredients that exhib...

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Main Authors: Jiaying Zhu, Chenhuan Shentu, Qingling Meng, Sen Fan, Yunjia Tang, Mingjiang Mao, Xiaofeng Yuan
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-06-01
Series:Frontiers in Pharmacology
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Online Access:https://www.frontiersin.org/articles/10.3389/fphar.2025.1585748/full
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author Jiaying Zhu
Chenhuan Shentu
Qingling Meng
Sen Fan
Yunjia Tang
Mingjiang Mao
Xiaofeng Yuan
author_facet Jiaying Zhu
Chenhuan Shentu
Qingling Meng
Sen Fan
Yunjia Tang
Mingjiang Mao
Xiaofeng Yuan
author_sort Jiaying Zhu
collection DOAJ
description IntroductionUlcerative colitis (UC) is a chronic, non-specific inflammatory bowel disease (IBD) that severely impairs the quality of life of affected individuals. Astragalus membranaceus (Fisch.) Bge. [Fabaceae; Astragali radix] (AM), a widely used Chinese medicine, has active ingredients that exhibit significant anti-inflammatory effects. This study aimed to investigate the role of AM extract in alleviating dextran sulfate sodium (DSS)-induced colitis in mice.MethodsA UC model was established, and AM extract was orally administered to evaluate its role in the treatment of colitis in mice. The effects of AM extract on colitis mice were subsequently investigated via 16S rDNA profiling, as well as short-chain fatty acids (SCFAs) and bile acids (BAs) sequencing. In addition, network pharmacology approaches and supplementary validation experiments were conducted to elucidate the underlying mechanisms of action.ResultsAM extract notably alleviated UC-related symptoms, promoted the restoration of intestinal barrier integrity, and suppressed inflammation. Concurrently, it contributed to the rebalancing of the gut microbiota and normalization of both SCFAs and BAs metabolic processes. Mechanistic investigations integrating network pharmacology and experimental validation revealed that the beneficial effects of AM extract are likely mediated through the regulation of the PI3K/AKT signaling pathway.DiscussionOur study demonstrated that the AM extract effectively alleviated UC. The extract was shown to modulate microbial dysbiosis triggered by DSS and promote the generation of beneficial metabolites. Subsequent analyses confirmed that these effects are mediated through activation of the PI3K/AKT signaling pathway. Collectively, these findings offer novel insights into treatment strategies for UC.
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spelling doaj-art-e14d20fadd2f45f9a67d2ef0db9d17932025-08-20T02:05:20ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-06-011610.3389/fphar.2025.15857481585748Astragalus membranaceus extract attenuates ulcerative colitis by integrating multiomics and the PI3K/AKT signaling pathwayJiaying Zhu0Chenhuan Shentu1Qingling Meng2Sen Fan3Yunjia Tang4Mingjiang Mao5Xiaofeng Yuan6School of Life Sciences, Zhejiang Chinese Medical University, Hangzhou, ChinaSchool of Life Sciences, Zhejiang Chinese Medical University, Hangzhou, ChinaSchool of Life Sciences, Zhejiang Chinese Medical University, Hangzhou, ChinaSchool of Life Sciences, Zhejiang Chinese Medical University, Hangzhou, ChinaFuture Health Laboratory, Innovation Center of Yangtze River Delta, Zhejiang University, Jiaxing, ChinaSchool of Life Sciences, Zhejiang Chinese Medical University, Hangzhou, ChinaSchool of Life Sciences, Zhejiang Chinese Medical University, Hangzhou, ChinaIntroductionUlcerative colitis (UC) is a chronic, non-specific inflammatory bowel disease (IBD) that severely impairs the quality of life of affected individuals. Astragalus membranaceus (Fisch.) Bge. [Fabaceae; Astragali radix] (AM), a widely used Chinese medicine, has active ingredients that exhibit significant anti-inflammatory effects. This study aimed to investigate the role of AM extract in alleviating dextran sulfate sodium (DSS)-induced colitis in mice.MethodsA UC model was established, and AM extract was orally administered to evaluate its role in the treatment of colitis in mice. The effects of AM extract on colitis mice were subsequently investigated via 16S rDNA profiling, as well as short-chain fatty acids (SCFAs) and bile acids (BAs) sequencing. In addition, network pharmacology approaches and supplementary validation experiments were conducted to elucidate the underlying mechanisms of action.ResultsAM extract notably alleviated UC-related symptoms, promoted the restoration of intestinal barrier integrity, and suppressed inflammation. Concurrently, it contributed to the rebalancing of the gut microbiota and normalization of both SCFAs and BAs metabolic processes. Mechanistic investigations integrating network pharmacology and experimental validation revealed that the beneficial effects of AM extract are likely mediated through the regulation of the PI3K/AKT signaling pathway.DiscussionOur study demonstrated that the AM extract effectively alleviated UC. The extract was shown to modulate microbial dysbiosis triggered by DSS and promote the generation of beneficial metabolites. Subsequent analyses confirmed that these effects are mediated through activation of the PI3K/AKT signaling pathway. Collectively, these findings offer novel insights into treatment strategies for UC.https://www.frontiersin.org/articles/10.3389/fphar.2025.1585748/fullulcerative colitisAstragalus membranaceusmicrobial dysbiosismetabolitesPI3K/Akt signaling pathway
spellingShingle Jiaying Zhu
Chenhuan Shentu
Qingling Meng
Sen Fan
Yunjia Tang
Mingjiang Mao
Xiaofeng Yuan
Astragalus membranaceus extract attenuates ulcerative colitis by integrating multiomics and the PI3K/AKT signaling pathway
Frontiers in Pharmacology
ulcerative colitis
Astragalus membranaceus
microbial dysbiosis
metabolites
PI3K/Akt signaling pathway
title Astragalus membranaceus extract attenuates ulcerative colitis by integrating multiomics and the PI3K/AKT signaling pathway
title_full Astragalus membranaceus extract attenuates ulcerative colitis by integrating multiomics and the PI3K/AKT signaling pathway
title_fullStr Astragalus membranaceus extract attenuates ulcerative colitis by integrating multiomics and the PI3K/AKT signaling pathway
title_full_unstemmed Astragalus membranaceus extract attenuates ulcerative colitis by integrating multiomics and the PI3K/AKT signaling pathway
title_short Astragalus membranaceus extract attenuates ulcerative colitis by integrating multiomics and the PI3K/AKT signaling pathway
title_sort astragalus membranaceus extract attenuates ulcerative colitis by integrating multiomics and the pi3k akt signaling pathway
topic ulcerative colitis
Astragalus membranaceus
microbial dysbiosis
metabolites
PI3K/Akt signaling pathway
url https://www.frontiersin.org/articles/10.3389/fphar.2025.1585748/full
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