{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T06:34:25Z","timestamp":1777012465608,"version":"3.51.4"},"reference-count":97,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T00:00:00Z","timestamp":1760572800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005297","name":"Medical University of Bia\u0142ystok","doi-asserted-by":"crossref","award":["B.SUB.23.154"],"award-info":[{"award-number":["B.SUB.23.154"]}],"id":[{"id":"10.13039\/501100005297","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100005297","name":"Medical University of Bia\u0142ystok","doi-asserted-by":"crossref","award":["B.SUB.24.152"],"award-info":[{"award-number":["B.SUB.24.152"]}],"id":[{"id":"10.13039\/501100005297","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Dietary polyphenols are recognized as crucial modulators of gastrointestinal motility, holding therapeutic promise for conditions like irritable bowel syndrome, postoperative ileus, and functional dyspepsia. However, their reported effects are heterogeneous, ranging from spasmolytic to prokinetic. This review aims to clarify these inconsistencies by synthesizing experimental evidence on structure\u2013activity relationships and underlying mechanisms. Relevant publications were identified in PubMed and Google Scholar using terms related to polyphenols and gastrointestinal motility. References were selected for relevance, and the narrative review integrates findings from in vitro, ex vivo, in vivo, and clinical studies. Across various experimental models, polyphenols function as multi-target modulators of gastrointestinal smooth muscle. The primary mechanisms identified involve the blockade of voltage-dependent L-type Ca2+ channels, activation of K+ channels (BK, KATP), and modulation of the NO\/cGMP and cAMP\/PKA pathways. Flavones and multiple flavonols consistently demonstrate spasmolytic activity via Ca2+ channel antagonism. In contrast, flavanones engage BK and KATP channels to induce membrane hyperpolarization. Complex extracts from plants like ginger and turmeric exhibit mixed pro- or antimotility effects, reflecting the diverse profiles of their constituent compounds. While robust ex vivo pharmacology and some in vivo and human data exist, a high degree of dataset heterogeneity and inconsistent reporting impedes direct translational efforts. Polyphenols are promising multi-mechanistic modulators of gastrointestinal motility with clear structure\u2013activity patterns. To advance their clinical application, future research must focus on establishing standardized in vivo pharmacokinetics, conducting targeted structure\u2013activity studies, employing bioassay-guided fractionation, and designing rigorous clinical trials.<\/jats:p>","DOI":"10.3390\/ph18101564","type":"journal-article","created":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T16:33:22Z","timestamp":1760632402000},"page":"1564","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Polyphenols as Modulators of Gastrointestinal Motility: Mechanistic Insights from Multi-Model Studies"],"prefix":"10.3390","volume":"18","author":[{"given":"Andrzej","family":"Chomentowski","sequence":"first","affiliation":[{"name":"Department of Biophysics, Faculty of Medicine, Medical University of Bialystok, 15-222 Bialystok, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0645-7020","authenticated-orcid":false,"given":"Krzysztof","family":"Drygalski","sequence":"additional","affiliation":[{"name":"Division of Hypertension & Diabetology, Faculty of Medicine, Medical University of Gdansk, 80-307 Gdansk, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0250-8698","authenticated-orcid":false,"given":"Tomasz","family":"Kleszczewski","sequence":"additional","affiliation":[{"name":"Department of Biophysics, Faculty of Medicine, Medical University of Bialystok, 15-222 Bialystok, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marta","family":"Berczy\u0144ska","sequence":"additional","affiliation":[{"name":"Department of Biophysics, Faculty of Medicine, Medical University of Bialystok, 15-222 Bialystok, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9594-8173","authenticated-orcid":false,"given":"Marzena","family":"Tylicka","sequence":"additional","affiliation":[{"name":"Department of Biophysics, Faculty of Medicine, Medical University of Bialystok, 15-222 Bialystok, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2404-6065","authenticated-orcid":false,"given":"Jacek","family":"Kapa\u0142a","sequence":"additional","affiliation":[{"name":"Department of Biophysics, Faculty of Medicine, Medical University of Bialystok, 15-222 Bialystok, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Agnieszka","family":"Raciborska","sequence":"additional","affiliation":[{"name":"Department of Biophysics, Faculty of Medicine, Medical University of Bialystok, 15-222 Bialystok, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-7271-9025","authenticated-orcid":false,"given":"Przemys\u0142aw","family":"Zubrzycki","sequence":"additional","affiliation":[{"name":"2nd Clinical Department of General, Gastroenterological and Oncological Surgery, Medical University of Bialystok, 15-222 Bialystok, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hady Razak","family":"Hady","sequence":"additional","affiliation":[{"name":"2nd Clinical Department of General, Gastroenterological and Oncological Surgery, Medical University of Bialystok, 15-222 Bialystok, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1051-7906","authenticated-orcid":false,"given":"Beata","family":"Modzelewska","sequence":"additional","affiliation":[{"name":"Department of Biophysics, Faculty of Medicine, Medical University of Bialystok, 15-222 Bialystok, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1675","DOI":"10.1016\/S0140-6736(20)31548-8","article-title":"Irritable Bowel Syndrome","volume":"396","author":"Ford","year":"2020","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Singh, R., Zogg, H., Ghoshal, U.C., and Ro, S. 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