{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T14:06:54Z","timestamp":1787580414616,"version":"build-2736575974"},"reference-count":52,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T00:00:00Z","timestamp":1760486400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["RS-2021-NR065896 2022R1C1C1004937"],"award-info":[{"award-number":["RS-2021-NR065896 2022R1C1C1004937"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003712","name":"Korea Food Research Institute","doi-asserted-by":"publisher","award":["E0210201-05"],"award-info":[{"award-number":["E0210201-05"]}],"id":[{"id":"10.13039\/501100003712","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec><jats:title>Purpose<\/jats:title><jats:p>Irritable bowel syndrome (IBS) is a prevalent gastrointestinal disorder with few effective long-term treatments. This study investigated the therapeutic potential of <jats:italic>Poncirus fructus<\/jats:italic> extract (PFE) for IBS-like symptoms, focusing on interstitial cells of Cajal (ICCs), visceral pain\u2013related ion channels, inflammation, and gut microbiota.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A zymosan-induced colitis mouse model was employed to mimic IBS-associated inflammation and pain. Electrophysiological recordings were performed in murine colonic ICCs and HEK293T cells overexpressing TRPV1, TRPV4, TRPA1, NaV1.5, or NaV1.7 channels. Additional analyses included histology, TNF-\u03b1 measurement, behavioral pain assessments, and gut microbiota profiling.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>PFE depolarized ICC pacemaker potentials in a dose-dependent manner through HCN channel activation and M3 muscarinic receptor\u2013mediated PLC-PKC signaling involving p38 MAPK and JNK pathways. <jats:italic>In vivo<\/jats:italic>, PFE improved colon length, reduced tissue inflammation and damage, lowered TNF-\u03b1 levels, and alleviated pain-related behaviors in zymosan-treated mice. Gut microbiota analysis revealed increased abundance of Lachnospiraceae following PFE treatment. Electrophysiology showed that PFE inhibited TRPV1 and NaV1.5\/1.7 currents, enhanced TRPV4 current, and had no effect on TRPA1 current.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>PFE exerts multi-target effects by modulating ICC activity, suppressing inflammation, and regulating key ion channels involved in visceral pain. These findings suggest that PFE has therapeutic potential for the management of IBS symptoms.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fphar.2025.1639592","type":"journal-article","created":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T09:52:16Z","timestamp":1760521936000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Therapeutic effects of Poncirus fructus on colonic dysfunction and visceral pain in a zymosan-induced irritable bowel syndrome mouse model through interstitial cells of Cajal and ion channel modulation"],"prefix":"10.3389","volume":"16","author":[{"given":"Na Ri","family":"Choi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seok-Jae","family":"Ko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Woo-Gyun","family":"Choi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daehwa","family":"Jung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sang Chan","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong Wook","family":"Lim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun Tai","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joo Han","family":"Woo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae-Woo","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Byung Joo","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,10,15]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"3296","DOI":"10.1007\/s11064-023-03983-z","article-title":"Capsaicin, the vanilloid receptor TRPV1 agonist in neuroprotection: mechanisms involved and significance","volume":"48","author":"Abdel-Salam","year":"2023","journal-title":"Neurochem. 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