{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T18:59:00Z","timestamp":1785437940952,"version":"3.56.0"},"reference-count":171,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T00:00:00Z","timestamp":1776729600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004663","name":"National Science and Technology Council","doi-asserted-by":"publisher","award":["NSTC-112-2923-B-006-0016-028"],"award-info":[{"award-number":["NSTC-112-2923-B-006-0016-028"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]},{"award":["NSTC-112-2923-B-006-0016-028"],"award-info":[{"award-number":["NSTC-112-2923-B-006-0016-028"]}],"id":[{"id":"https:\/\/ror.org\/00wnb9798","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100020872","name":"An Nan Hospital","doi-asserted-by":"crossref","award":["ANHRF114-06"],"award-info":[{"award-number":["ANHRF114-06"]}],"id":[{"id":"10.13039\/501100020872","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100020872","name":"An Nan Hospital","doi-asserted-by":"crossref","award":["ANHRF114-43"],"award-info":[{"award-number":["ANHRF114-43"]}],"id":[{"id":"10.13039\/501100020872","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100020872","name":"An Nan Hospital","doi-asserted-by":"crossref","award":["ANHRF114-49"],"award-info":[{"award-number":["ANHRF114-49"]}],"id":[{"id":"10.13039\/501100020872","id-type":"DOI","asserted-by":"crossref"}]},{"award":["ANHRF114-06"],"award-info":[{"award-number":["ANHRF114-06"]}],"id":[{"id":"https:\/\/ror.org\/00ew3x319","id-type":"ROR","asserted-by":"publisher"}]},{"award":["ANHRF114-43"],"award-info":[{"award-number":["ANHRF114-43"]}],"id":[{"id":"https:\/\/ror.org\/00ew3x319","id-type":"ROR","asserted-by":"publisher"}]},{"award":["ANHRF114-49"],"award-info":[{"award-number":["ANHRF114-49"]}],"id":[{"id":"https:\/\/ror.org\/00ew3x319","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Lithuania-Latvia-Taiwan collaborative project"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>This review provides a comprehensive overview of the modulatory actions of plant-derived constituents on membrane ion channels in various cell types. Among their diverse bioactivities, ion channel regulation\u2014governing membrane excitability, signal transduction, and cellular homeostasis\u2014has emerged as a critical mechanistic basis for their pharmacological effects. Twenty-four representative phytoconstituents are discussed and classified into five major categories based on their structural features: alkaloids, terpenoids, lignans and acetogenins, polyphenols, and other aromatic and conjugated compounds. Across these categories, the reviewed compounds exhibit distinct and often highly specific effects on the amplitude and gating kinetics of multiple ionic currents, including voltage-gated Na+ currents (INa), delayed-rectifier K+ currents (IK(DR)), M-type K+ currents (IK(M)), hyperpolarization-activated cation currents (Ih), erg-mediated K+ currents (IK(erg)), inwardly rectifying K+ currents, and Ca2+-activated K+ currents (IK(Ca)). Alkaloids predominantly suppress voltage-gated K+ currents, with notable exceptions such as aconitine, which alters the properties of both INa and IK(DR), thereby contributing to its proarrhythmic toxicity. Terpenoids, including cannabidiol, croton diterpenoids, lutein, thymol, and triptolide, exert multifaceted effects on IK(M), Ih, inwardly rectifying K+ currents, and Ca2+-activated K+ channels. Lignans and acetogenins, such as gomisin A, honokiol, sesamin, and squamocin, primarily modulate INa, Ih, and IK(Ca), with several compounds demonstrating strong links between ion-channel modulation and anti-neoplastic or neuroprotective actions. Polyphenolic compounds, including curcumin, eugenol, resveratrol, gastrodigenin, gastrodin, and pterostilbene, display diverse ion-channel targeting profiles, influencing multiple Na+ and K+ channel subtypes. Other aromatic or conjugated compounds, such as isoplumbagin, plumbagin, and verteporfin, regulate IK(erg) and IK(Ca), potentially contributing to both therapeutic efficacy and adverse effects. Collectively, the compound-specific modulation of current amplitude and gating kinetics offers valuable mechanistic insight into the pharmacological and toxicological significance of plant-derived natural products, highlighting the functional role of ion channel evaluation in guiding their therapeutic development and ensuring safety assessment.<\/jats:p>","DOI":"10.3390\/molecules31081360","type":"journal-article","created":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T11:42:45Z","timestamp":1776771765000},"page":"1360","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Modulatory Effects of Bioactive Phytoconstituents on the Amplitude and Gating Properties of Membrane Ion Channels"],"prefix":"10.3390","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5208-3253","authenticated-orcid":false,"given":"Sheng-Nan","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Medical Research, An Nan Hospital, China Medical University, No. 66, Section 2, Changhe Road, An Nan District, Tainan 70965, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5936-1789","authenticated-orcid":false,"given":"Guglielmina","family":"Froldi","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Largo E, Meneghetti 2, 35131 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7524-4363","authenticated-orcid":false,"given":"Ya-Jean","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Senior Service Industry Management, Minghsin University of Science and Technology, 1 Xinxing Road, Xinxfen Township, Hsinchu 304001, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5395-923X","authenticated-orcid":false,"given":"Rasa","family":"Liutkevi\u010dien\u0117","sequence":"additional","affiliation":[{"name":"Laboratory of Ophthalmology, Institute of Neuroscience, Lithuanian University of Health Sciences, 50106 Kaunas, Lithuania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Rao, R., Mohammed, C., Alschuler, L., Pomeranz Krummel, D.A., and Sengupta, S. 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