{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T05:13:38Z","timestamp":1783660418505,"version":"3.55.0"},"reference-count":41,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T00:00:00Z","timestamp":1783641600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Chronic atrophic gastritis (CAG) is a precancerous gastric lesion characterized by persistent inflammatory injury, glandular atrophy, and impairment of gastric mucosal barrier-associated integrity. Huangjin Shuangshen Decoction (HJSS) has shown therapeutic potential in gastritis-related disorders, but its effects on CAG and the underlying mechanism remain unclear. This study investigated whether HJSS alleviates CAG by modulating inflammation-associated barrier dysfunction.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      CAG was induced in mice by MNNG combined with ranitidine and irregular feeding, followed by treatment with different doses of HJSS, with folic acid as a positive control. Histopathology, gastric function indices, inflammatory mediators, apoptosis-related markers, and barrier-associated molecules were assessed\n                      <jats:italic>in vivo<\/jats:italic>\n                      . MNNG-injured GES-1 cells treated with HJSS-medicated serum were used for\n                      <jats:italic>in vitro<\/jats:italic>\n                      validation. Transcriptomic analysis, network pharmacology, and pharmacological inhibition were integrated to explore the underlying mechanisms.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      HJSS alleviated gastric mucosal atrophy and histopathological injury, improved gastric functional impairment, reduced inflammatory burden, and attenuated apoptosis-associated epithelial injury in experimental CAG. HJSS also promoted the recovery of gastric mucosal barrier-associated molecules, including CFTR, ZO-1, MUC5AC, Occludin, and Claudin-1. Integrated transcriptomic and network pharmacology analyses highlighted an inflammation\u2013barrier framework involving TNF-related signaling and CFTR-associated regulation.\n                      <jats:italic>In vitro<\/jats:italic>\n                      , HJSS mitigated MNNG-induced epithelial injury, whereas CFTR inhibition attenuated the HJSS-associated restoration of CFTR and ZO-1. HJSS was further associated with suppression of TNF\/NF-\u03baB signaling and reduced p65 nuclear translocation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>HJSS alleviates MNNG-induced CAG by attenuating inflammatory injury and promoting the recovery of gastric mucosal barrier-associated molecular features. Its protective effects are associated with suppression of TNF\/NF-\u03baB signaling and involvement of CFTR-associated regulation, supporting an inflammation\u2013barrier mechanism underlying the action of HJSS in CAG.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1848471","type":"journal-article","created":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T04:24:01Z","timestamp":1783657441000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Huangjin Shuangshen decoction alleviates chronic atrophic gastritis by suppressing TNF\/NF-\u03baB signaling and promoting CFTR-associated gastric mucosal barrier repair"],"prefix":"10.3389","volume":"17","author":[{"given":"Shuo","family":"Zhang","sequence":"first","affiliation":[{"name":"School of Basic Medical Sciences, Zhejiang Chinese Medical University","place":["Hangzhou, China"]},{"name":"Zhejiang Key Laboratory of Blood-Stasis-Toxin Syndrome, Zhejiang Chinese Medical University","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuya","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences, Zhejiang Chinese Medical University","place":["Hangzhou, China"]},{"name":"Zhejiang Key Laboratory of Blood-Stasis-Toxin Syndrome, Zhejiang Chinese Medical University","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengyi","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences, Zhejiang Chinese Medical University","place":["Hangzhou, China"]},{"name":"Zhejiang Key Laboratory of Blood-Stasis-Toxin Syndrome, Zhejiang Chinese Medical University","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xueru","family":"Huang","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences, Zhejiang Chinese Medical University","place":["Hangzhou, China"]},{"name":"Zhejiang Key Laboratory of Blood-Stasis-Toxin Syndrome, Zhejiang Chinese Medical University","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Huang","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences, Zhejiang Chinese Medical University","place":["Hangzhou, China"]},{"name":"Zhejiang Key Laboratory of Blood-Stasis-Toxin Syndrome, Zhejiang Chinese Medical University","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Jiang","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences, Zhejiang Chinese Medical University","place":["Hangzhou, China"]},{"name":"Zhejiang Key Laboratory of Blood-Stasis-Toxin Syndrome, Zhejiang Chinese Medical University","place":["Hangzhou, China"]},{"name":"Traditional Chinese Medicine \u201cPreventing Disease\u201d Wisdom Health Project Research Center of Zhejiang","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangji","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences, Zhejiang Chinese Medical University","place":["Hangzhou, China"]},{"name":"Zhejiang Key Laboratory of Blood-Stasis-Toxin Syndrome, Zhejiang Chinese Medical University","place":["Hangzhou, China"]},{"name":"Traditional Chinese Medicine \u201cPreventing Disease\u201d Wisdom Health Project Research Center of Zhejiang","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,10]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gtc.2013.01.002","article-title":"Human gastric carcinogenesis: A multistep and multifactorial process--first American Cancer Society Award Lecture on cancer epidemiology and 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