{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T06:23:57Z","timestamp":1787207037075,"version":"build-2736575974"},"reference-count":29,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T00:00:00Z","timestamp":1787184000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Chronic inflammation-driven gastric precancerous lesions (GPL) are characterized by progressive immune remodeling toward an immunosuppressive state, yet effective chemopreventive agents targeting this process remain scarce. Here, we identify asiatic acid (AA), a natural pentacyclic triterpenoid, as a STING\u2011binding compound that contributes to reshaping the gastric immune microenvironment and interfering with the Correa cascade.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Using a rat model of MNNG\u2011induced GPL (atrophy, intestinal metaplasia, dysplasia) and MNNG\u2011treated GES\u20111 cells, we assessed histopathological damage, systemic pro\u2011inflammatory cytokines (TNF, IL\u20116, MCP1), and gastric physiological function. STING binding was evaluated by surface plasmon resonance (SPR) with KD measurement and 100 ns molecular dynamics simulations. The cGAS\u2013STING\u2013TBK1\u2013IRF3 axis was examined\n                      <jats:italic>in vivo<\/jats:italic>\n                      and\n                      <jats:italic>in vitro<\/jats:italic>\n                      . Gut microbiota was analyzed by 16S rRNA sequencing, and the Nrf2\u2013Keap1 antioxidant pathway, mitochondrial membrane potential, and oxidative stress were measured. Rescue experiments were performed using the STING agonist cGAMP.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>AA ameliorated histopathological damage, exerted regulatory effects on systemic pro\u2011inflammatory cytokines with a non\u2011linear dose\u2011response pattern, and improved gastric physiological function. Mechanistically, AA directly bound to STING with a KD of 4.0 \u03bcM and maintained a stable conformation in simulations, suppressing aberrant activation of the cGAS\u2013STING\u2013TBK1\u2013IRF3 axis. AA also reversed gut microbiota dysbiosis (notably reducing pro\u2011inflammatory Erysipelotrichales), restored the Nrf2\u2013Keap1 pathway, improved mitochondrial membrane potential, and reduced oxidative stress. Rescue experiments with cGAMP partially abolished AA\u2019s protective effects, supporting the functional involvement of STING signaling in AA\u2019s actions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Collectively, AA interrupts the vicious \u201cmicrobiota\u2013oxidative stress\u2013STING\u201d loop in a STING\u2011dependent manner and contributes to remodeling the precancerous immune microenvironment, positioning it as a promising chemopreventive candidate targeting the earliest phase of gastric carcinogenesis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1896372","type":"journal-article","created":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T05:28:55Z","timestamp":1787203735000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Asiatic acid remodels the gastric precancerous immune microenvironment by targeting STING"],"prefix":"10.3389","volume":"17","author":[{"given":"Haotian","family":"Li","sequence":"first","affiliation":[{"name":"Institute of Basic Theory of Traditional Chinese Medicine, China Academy of Chinese Medical Sciences","place":["Beijing, China"]},{"name":"Wangjing Hospital, China Academy of Chinese Medical Sciences","place":["Beijing, China"]},{"name":"Department of Digestive Disorders, Beijing Key Laboratory of Diagnosis and Treatment of Functional Gastrointestinal Diseases of Traditional Chinese Medicine, Wangjing Hospital, China Academy of Chinese Medical Sciences","place":["Beijing, China"]},{"name":"Beijing University of Chinese Medicine","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Shen","sequence":"additional","affiliation":[{"name":"Institute of Basic Theory of Traditional Chinese Medicine, China Academy of Chinese Medical Sciences","place":["Beijing, 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China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Man","family":"Meng","sequence":"additional","affiliation":[{"name":"Wangjing Hospital, China Academy of Chinese Medical Sciences","place":["Beijing, China"]},{"name":"Department of Digestive Disorders, Beijing Key Laboratory of Diagnosis and Treatment of Functional Gastrointestinal Diseases of Traditional Chinese Medicine, Wangjing Hospital, China Academy of Chinese Medical Sciences","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianqin","family":"Yang","sequence":"additional","affiliation":[{"name":"Wangjing Hospital, China Academy of Chinese Medical Sciences","place":["Beijing, China"]},{"name":"Department of Digestive Disorders, Beijing Key Laboratory of Diagnosis and Treatment of Functional Gastrointestinal Diseases of Traditional Chinese Medicine, Wangjing Hospital, China Academy of Chinese Medical Sciences","place":["Beijing, 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