{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T07:16:33Z","timestamp":1781507793992,"version":"3.54.1"},"reference-count":48,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2022,12,2]],"date-time":"2022-12-02T00:00:00Z","timestamp":1669939200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Nobiletin (NOB) has attracted much attention owing to its outstanding bioactivities. This study aimed to investigate its anti-arrhythmic effect through electrophysiological and molecular docking studies. We assessed the anti-arrhythmic effects of NOB using aconitine-induced ventricular arrhythmia in a rat model and the electrophysiological effects of NOB on rat cardiomyocytes utilizing whole-cell patch-clamp techniques. Moreover, we investigated the binding characters of NOB with rNav1.5, rNav1.5\/QQQ, and hNaV1.5 via docking analysis, comparing them with amiodarone and aconitine. NOB pretreatment delayed susceptibility to ventricular premature and ventricular tachycardia and decreased the incidence of fatal ventricular fibrillation. Whole-cell patch-clamp assays demonstrated that the peak current density of the voltage-gated Na+ channel current was reversibly reduced by NOB in a concentration-dependent manner. The steady-state activation and recovery curves were shifted in the positive direction along the voltage axis, and the steady-state inactivation curve was shifted in the negative direction along the voltage axis, as shown by gating kinetics. The molecular docking study showed NOB formed a \u03c0-\u03c0 stacking interaction with rNav1.5 and rNav1.5\/QQQ upon Phe-1762, which is the homolog to Phe-1760 in hNaV1.5 and plays an important role in antiarrhythmic action This study reveals that NOB may act as a class I sodium channel anti-arrhythmia agent.<\/jats:p>","DOI":"10.3390\/ijms232315175","type":"journal-article","created":{"date-parts":[[2022,12,5]],"date-time":"2022-12-05T01:42:21Z","timestamp":1670204541000},"page":"15175","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Inhibitory Effects of Nobiletin on Voltage-Gated Na+ Channel in Rat Ventricular Myocytes Based on Electrophysiological Analysis and Molecular Docking Method"],"prefix":"10.3390","volume":"23","author":[{"given":"Youwei","family":"Gu","sequence":"first","affiliation":[{"name":"Department of Pharmacology, School of Medicine, Yangzhou University, Yangzhou 225009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jieru","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Medicine, Yangzhou University, Yangzhou 225009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengting","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Medicine, Yangzhou University, Yangzhou 225009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei","family":"Zhong","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Medicine, Yangzhou University, Yangzhou 225009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3107-9888","authenticated-orcid":false,"given":"Jie","family":"Xiang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Medicine, Yangzhou University, Yangzhou 225009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengxin","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Medicine, Yangzhou University, Yangzhou 225009, China"},{"name":"Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, China"},{"name":"Jingsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Yangzhou 225001, China"},{"name":"Jiangsu Key Laboratory of Experimental & Translational Non-Coding RNA Research, Yangzhou 225009, China"},{"name":"Yeda Institute of Gene and Cell Therapy, Taizhou 318000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1007\/s00424-020-02505-y","article-title":"The role of calcium homeostasis remodeling in inherited cardiac arrhythmia syndromes","volume":"473","author":"Hamilton","year":"2021","journal-title":"Pflugers Arch."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1016\/j.semnephrol.2013.04.003","article-title":"Role of circadian rhythms in potassium homeostasis","volume":"33","author":"Gumz","year":"2013","journal-title":"Semin. 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