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This study aimed to explore the mechanism of acidic bile\u2010mediated LPRD progression and the therapeutic potential of isoquercitrin. An acidic bile\u2010stimulated HHPC cell model and a pyloric ligation\u2010induced rat LPRD model were established. High\u2010throughput screening was used to identify optimal active monomers. Multiple molecular biological assays, molecular docking, microscale thermophoresis, and luciferase reporter assays were performed to verify protein binding and signaling regulation. Gradient\u2010dose isoquercitrin treatment was applied for in\u00a0vitro and in\u00a0vivo validation. Pathologically, acidic bile (pH\u20094.0) disrupted pharyngeal epithelial barrier integrity, decreased E\u2010cadherin expression, and induced EMT by activating the ASIC3\/RhoA\/\u03b2\u2010catenin positive feedback loop, in which \u03b2\u2010catenin\/TCF\/LEF further transcriptionally upregulated ASIC3. High\u2010throughput screening confirmed isoquercitrin (IC50\u2009=\u200934.2\u2009\u03bcM) as the optimal anti\u2010EMT monomer. Mechanistically, isoquercitrin directly bound the N426\/S425 sites of \u03b2\u2010catenin, restrained \u03b2\u2010catenin nuclear translocation, and thereby blocked the positive feedback cascade, restored epithelial barrier homeostasis, and reversed bile\u2010induced EMT. Consistently, in\u00a0vivo LPRD models verified that isoquercitrin dose\u2010dependently attenuated inflammatory infiltration, rescued pharyngeal tissue structural damage, downregulated ASIC3, and recovered E\u2010cadherin expression. In conclusion, isoquercitrin ameliorates LPRD by inhibiting EMT via targeting the ASIC3\/RhoA\/\u03b2\u2010catenin feedback pathway. These findings identify isoquercitrin as a novel therapeutic candidate for LPRD.<\/jats:p>","DOI":"10.1111\/jgh.70764","type":"journal-article","created":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T23:36:06Z","timestamp":1790811366000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Isoquercitrin Inhibits Laryngopharyngeal Reflux Disease\u2010Related Pharyngeal EMT by Regulating the ASIC3\/RhoA\/\u03b2\u2010Catenin Positive Feedback Signaling Pathway"],"prefix":"10.1111","author":[{"given":"Qi","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Geriatrics, Institute of Gerontology Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology  Wuhan China"},{"name":"Key Laboratory of Vascular Aging, Ministry of Education Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology  Wuhan 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