ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Ethnopharmacology
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1639592
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
Provisionally accepted
Na Ri Choi1
Seok-Jae Ko2Woo-Gyun Choi1Daehwa Jung3Sang Chan Kim3
Dong Wook Lim4
Yun Tai Kim4
JOOHAN WOO5
Jae-Woo Park6*
BYUNG JOO KIM1*- 1Pusan National University, Busan, Republic of Korea
- 2Kyung Hee University College of Korean Medicine, Seoul, Republic of Korea
- 3Daegu Haany University, Gyeongsan-si, Republic of Korea
- 4Korea Food Research Institute, Wanju-gun, Republic of Korea
- 5Dongguk University College of Medicine, Gyeongju-si, Republic of Korea
- 6Kyung Hee University, Dongdaemun-gu, Republic of Korea
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Purpose: Irritable bowel syndrome (IBS) is a prevalent gastrointestinal disorder with few effective long-term treatments. This study investigated the therapeutic potential of Poncirus fructus extract (PFE) for IBS-like symptoms, focusing on interstitial cells of Cajal (ICCs), visceral pain–related ion channels, inflammation, and gut microbiota. Methods: 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-α measurement, behavioral pain assessments, and gut microbiota profiling. Results: PFE depolarized ICC pacemaker potentials in a dose-dependent manner through HCN channel activation and M3 muscarinic receptor–mediated PLC-PKC signaling involving p38 MAPK and JNK pathways. In vivo, PFE improved colon length, reduced tissue inflammation and damage, lowered TNF-α 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. Conclusion: 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.
Keywords: irritable, bowel, syndrome, Poncirus, Fructus, zymosan-induced, Colitis, Electrophysiology
Received: 02 Jun 2025; Accepted: 03 Oct 2025.
Copyright: © 2025 Choi, Ko, Choi, Jung, Kim, Lim, Kim, WOO, Park and KIM. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Jae-Woo Park, pjw2907@khu.ac.kr
BYUNG JOO KIM, vision@pusan.ac.kr
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.