{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,13]],"date-time":"2026-11-13T08:19:41Z","timestamp":1794557981243,"version":"4.9.1"},"reference-count":31,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2023,5,30]],"date-time":"2023-05-30T00:00:00Z","timestamp":1685404800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82270326"],"award-info":[{"award-number":["82270326"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2023,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Sudden cardiac death (SCD) remains a major cause of global mortality. In addition to modern interventions, botanical folk medicines have long been used to treat cardiovascular disease, although the efficacy and underlying mechanisms are often unresolved. Aloperine, a bioactive quinolizidine alkaloid isolated from\n                    <jats:italic>Sophora alopecuroides<\/jats:italic>\n                    plants, exhibits antioxidant, anti\u2010inflammatory, antitumor, and vasorelaxant properties, but possible antiarrhythmic effects of aloperine in SCD are unclear. Here, we examined whether aloperine protects against ischemia and reperfusion injury\u2010associated lethal ventricular arrhythmia and sudden cardiac death. Rats were divided into sham, control, and aloperine groups, and reperfusion\u2010provoked ventricular arrhythmogenesis, cardiac damage markers, and signaling pathways quantified following left main coronary artery ischemia and reperfusion. In vitro studies of effects of aloperine on hERG and Kv4.3 cardiac voltage\u2010gated potassium (Kv) channels were performed using two\u2010electrode voltage clamp analysis of cloned channels expressed in\n                    <jats:italic>Xenopus laevis<\/jats:italic>\n                    oocytes. Aloperine pretreatment (10\u2009mg\/kg) did not affect baseline cardiac electrical stability; yet, it reduced ventricular arrhythmogenesis and susceptibility to SCD (mortality rate: control: 64.3%; aloperine: 0%) induced by reperfusion injury. Aloperine also reduced serum levels of LDH, CK\u2010MB, \u03b1\u2010HBDH, and cTnI post\u2010I\/R, and stimulated phosphorylation of ventricular ERK1\/2 and STAT\u20103, which are key components of RISK and SAFE signaling pathways. Inhibition of either ERK1\/2 (with U0126) or STAT\u20103 (with Ag490) abolished aloperine\u2010induced anti\u2010arrhythmic effects and ERK1\/2 and STAT\u20103 phosphorylation. Interestingly, while aloperine (100\u2009\u03bcM) had no effect on cloned Kv4.3 activity, aloperine (1\u2009\u03bcM and up) negative\u2010shifted the voltage dependence of hERG activation by ~10\u2009mV and increased peak hERG current by 35%. Thus, aloperine exerts striking anti\u2010arrhythmic effects against myocardial ischemia and reperfusion injury\u2010induced severe lethal ventricular arrhythmia and sudden cardiac death via the ERK1\/2\/STAT\u20103 signaling pathway, with potential additional contribution from increased cardiac myocyte repolarization capacity via augmented hERG activity.\n                  <\/jats:p>","DOI":"10.1096\/fj.202300253r","type":"journal-article","created":{"date-parts":[[2023,5,30]],"date-time":"2023-05-30T09:19:31Z","timestamp":1685438371000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["The plant\u2010derived alkaloid aloperine prevents ischemia\/reperfusion injury\u2010induced sudden cardiac death"],"prefix":"10.1096","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3642-9610","authenticated-orcid":false,"given":"Zhaoyang","family":"Hu","sequence":"first","affiliation":[{"name":"Laboratory of Anesthesia and Critical Care Medicine, National\u2010Local Joint Engineering Research Centre of Translational Medicine of Anesthesiology West China Hospital, Sichuan University  Chengdu Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaxue","family":"Li","sequence":"additional","affiliation":[{"name":"Laboratory of Anesthesia and Critical Care Medicine, National\u2010Local Joint Engineering Research Centre of Translational Medicine of Anesthesiology West China Hospital, Sichuan University  Chengdu Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quanhua","family":"Liu","sequence":"additional","affiliation":[{"name":"Laboratory of Anesthesia and Critical Care Medicine, National\u2010Local Joint Engineering Research Centre of Translational Medicine of Anesthesiology West China Hospital, Sichuan University  Chengdu Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0057-3541","authenticated-orcid":false,"given":"R\u00edan W.","family":"Manville","sequence":"additional","affiliation":[{"name":"Bioelectricity Laboratory, Department of Pharmacology, Department of Physiology and Biophysics School of Medicine, University of California  Irvine California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4552-496X","authenticated-orcid":false,"given":"Geoffrey W.","family":"Abbott","sequence":"additional","affiliation":[{"name":"Bioelectricity Laboratory, Department of Pharmacology, Department of Physiology and Biophysics School of Medicine, University of California  Irvine California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,5,30]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/europace\/euv319"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2019.112172"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-24565-y"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.3892\/etm.2018.5896"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.2119\/molmed.2015.00056"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1907511116"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1080\/21691401.2019.1699816"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1159\/000500761"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2017.02.033"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.8.150"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0030-1250256"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12933-017-0537-3"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCGENETICS.113.000315"},{"issue":"3","key":"e_1_2_9_15_1","first-page":"H747","article-title":"Measurement of heart rate and Q\u2010T interval in the conscious mouse. 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