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The incidence of CAG has been steadily increasing, yet effective pharmacological interventions remain unavailable. Asiatic acid (AA), a bioactive triterpenoid isolated from\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>Centella asiatica<\/jats:italic>\n                    <\/jats:styled-content>\n                    , has demonstrated anti\u2010inflammatory, antioxidant, and anticarcinogenic properties in various diseases. However, its role and underlying mechanism in CAG remain poorly understood. This study sought to clarify the therapeutic potential and molecular mechanisms of AA in CAG. GES\u20101 cells were exposed to N\u2010methyl\u2010N\u2010nitro\u2010N\u2010nitrosoguanidine (MNNG) to establish an in\u00a0vitro CAG cell model (MC cells). Concurrently, a CAG mouse model was generated using a combination of MNNG and ethanol. Both models were treated with different concentrations of AA to evaluate its effects on HRAS\/PI3K\/AKT\/GSK3\u03b2 axis\u2010mediated CAG. Furthermore, bioinformatics and proteomic analyses, followed by experimental validation, were applied to explore underlying mechanisms. AA significantly inhibited the proliferation and migration of MC cells and promoted apoptosis. Mechanistic studies revealed that the HRAS\/PI3K\/AKT\/GSK3\u03b2 signaling axis was aberrantly activated in CAG. In MC cells, knockdown of HRAS markedly attenuated the effect of AA; conversely, HRAS overexpression or treatment with the agonist 740Y\u2010P partially counteracted its efficacy. In\u00a0vivo experiments confirmed that AA markedly ameliorated gastric mucosal glandular atrophy, structural disorganization, and intestinal metaplasia. Furthermore, preliminary analyses suggested that AA may suppress GC progression via the same signaling pathway. AA alleviates CAG by suppressing the HRAS\/PI3K\/AKT\/GSK3\u03b2 signaling axis, thereby highlighting its therapeutic potential and providing a novel strategy for CAG treatment.\n                  <\/jats:p>","DOI":"10.1002\/ptr.70265","type":"journal-article","created":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T02:44:16Z","timestamp":1770777856000},"page":"2210-2229","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Asiatic Acid Ameliorates\n                    <scp>MNNG<\/scp>\n                    \u2010Induced Chronic Atrophic Gastritis by Inhibiting the Activation of the\n                    <scp>HRAS<\/scp>\n                    \/\n                    <scp>PI3K<\/scp>\n                    \/\n                    <scp>AKT<\/scp>\n                    \/\n                    <scp>GSK3\u03b2<\/scp>\n                    Signaling Axis"],"prefix":"10.1002","volume":"40","author":[{"given":"Feifei","family":"Zhou","sequence":"first","affiliation":[{"name":"Department of Gastroenterology Shandong Provincial Hospital Affiliated to Shandong First Medical University  Jinan Shandong China"},{"name":"Medical Science and Technology Innovation Center Shandong First Medical University &amp; Shandong Academy of Medical Sciences  Jinan Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cuiyu","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Shandong Provincial Hospital Affiliated to Shandong First Medical University  Jinan Shandong China"},{"name":"Medical Science and Technology Innovation Center Shandong First Medical University &amp; Shandong Academy of Medical Sciences  Jinan Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanwan","family":"Yuan","sequence":"additional","affiliation":[{"name":"Innovative Institute of Chinese Medicine and Pharmacy Shandong University of Traditional Chinese Medicine  Jinan Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenkun","family":"Peng","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Shandong Provincial Hospital Affiliated to Shandong First Medical University  Jinan Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0076-5666","authenticated-orcid":false,"given":"Qianqian","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Shandong Provincial Hospital Affiliated to Shandong First Medical University  Jinan Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongli","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Shandong Provincial Hospital Affiliated to Shandong First Medical University  Jinan Shandong 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