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This study was aimed to figure out its antidiabetic mechanisms. The db\/db mice were treated with AS\u2010IV, and the metabolism phenotype and epithelial barrier permeability were tested. Trans\u2010epithelial resistance assay was performed in Caco\u20102 cells. Metagenomic sequencing was used to determine the gut microbiota composition and function. The content of short\u2010chain fatty acid (SCFA) in feces was determined using Agilent 8890\u20105977B GC\u2013MS. Despite increasing mice body weight, AS\u2010IV significantly reduced hyperglycemia in the db\/db mice, decreased the ratio of liver weight\/body weight, alleviated hepatic total cholesterol and triglyceride levels. AS\u2010IV reduced inflammation through suppressing pro\u2010inflammatory genes (\n                    <jats:italic>Il1b, Tnf, Ccl2<\/jats:italic>\n                    ) and elevating anti\u2010inflammatory genes (\n                    <jats:italic>Il10, Il4, Il13, Il33<\/jats:italic>\n                    ) in the colonic epithelium. AS\u2010IV also reversed the increased intestinal permeability and decreased expression of tight junction (TJ) proteins Claudin\u20101, ZO\u20101 in the db\/db mice and Claudin\u20101, Occludin in Caco\u20102 cells. Additionally, metagenomic sequencing showed AS\u2010IV altered composition and function of gut microbiota. The 80 species of gut microbiota were markedly changed, e.g., boosting of\n                    <jats:italic>Alistipes<\/jats:italic>\n                    spp. and\n                    <jats:italic>\n                      <jats:styled-content style=\"fixed-case\">Prevotella copri<\/jats:styled-content>\n                      ,\n                    <\/jats:italic>\n                    decreasing of relative abundance of\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>Ruminococcus gnavus<\/jats:italic>\n                    <\/jats:styled-content>\n                    and\n                    <jats:italic>Enterocloster bolteae<\/jats:italic>\n                    . AS\u2010IV upregulated the SCFA related pathway, increased the content of SCFA, upregulated the transcription levels of SCFA receptors (i.e., GPR41, GPR43 and GPR109a), thereby improved glucose metabolism in the db\/db mice. These findings demonstrate that AS\u2010IV exhibited favorable antidiabetic effects by improving glucose metabolism and altering intestinal microbiota symbiosis via repairing the damaged gut barrier. This study will provide valuable reference for the development of new antidiabetic drugs and medication of T2DM.\n                  <\/jats:p>","DOI":"10.1002\/ptr.70205","type":"journal-article","created":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T05:49:21Z","timestamp":1775627361000},"page":"5016-5029","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Astragaloside\n                    <scp>IV<\/scp>\n                    Exhibited Antidiabetic Effects by Improving Glucose Metabolism, Repairing Damaged Gut Barrier and Regulating Intestinal Microbiota"],"prefix":"10.1002","volume":"40","author":[{"given":"Xiaolei","family":"Yang","sequence":"first","affiliation":[{"name":"School of Pharmaceutical Sciences, State Key Laboratory of Advanced Drug Formulations for Overcoming Delivery Barriers Fudan University  Shanghai 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