{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T15:41:41Z","timestamp":1787499701342,"version":"build-2736575974"},"reference-count":53,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,2,6]],"date-time":"2025-02-06T00:00:00Z","timestamp":1738800000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Phytotherapy Research"],"published-print":{"date-parts":[[2025,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Myocardial ischemia\u2013reperfusion injury (MI\/RI) is a critical challenge for acute myocardial infarction therapy, as there is currently no ideal drug available. Glycogen synthase kinase 3 beta (GSK\u20103\u03b2) serves as an promising therapeutic target for treating MI\/RI. Our previous studies have demonstrated that\n                    <jats:italic>Ilex pubescens<\/jats:italic>\n                    ameliorates MI\/RI. The purpose of this study is to evaluate the therapeutic efficacy and potential mechanism of the screened GSK\u20103\u03b2 inhibitor from\n                    <jats:italic>Ilex pubescens<\/jats:italic>\n                    against MI\/RI. Three\u2010dimensional\u2010quantitative structure\u2013activity relationship (3D\u2010QSAR) modeling, molecular docking, the oxygen and glucose deprivation\/reperfusion (OGD\/R) and left anterior descending (LAD) artery ligation\u2010induced MI\/RI mice model, and western blotting analysis were used to screen and investigate the myocardial protective efficacy and mechanism. Here, we screened Pubescenoside D (PBD) as a GSK\u20103\u03b2 inhibitor with an IC50 value of 0.3769\u2009\u03bcM from\n                    <jats:italic>Ilex pubescens,<\/jats:italic>\n                    using 3D\u2010QSAR modeling, molecular docking, and kinase assay verification. Ile217, Leu88, Phe93, and Phe67 are the key binding sites for PBD and GSK\u20103\u03b2. PBD protects cardiomyocytes against MI\/RI in\u00a0vitro and in\u00a0vivo. Further mechanism studies show that PBD inhibits mitochondrial permeability transition pore (mPTP) opening by preventing GSK\u20103\u03b2\u2010mediated the dissociation of hexokinase2 (HK2) from the outer membrane of the mitochondria and enhances mitophagy by suppressing GSK\u20103\u03b2 activity, subsequently reducing cardiomyocyte apoptosis. Our findings shed light on the efficacy of PBD as a promising therapeutic agent in the treatment of MI\/RI targeting GSK\u20103\u03b2.\n                  <\/jats:p>","DOI":"10.1002\/ptr.8434","type":"journal-article","created":{"date-parts":[[2025,2,7]],"date-time":"2025-02-07T00:55:07Z","timestamp":1738889707000},"page":"1578-1591","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Pubescenoside D Ameliorates Myocardial Ischemia\u2013Reperfusion Injury via Preventing the Dissociation of\n                    <scp>HK2<\/scp>\n                    and Promoting Mitophagy by Targeting\n                    <scp>GSK<\/scp>\n                    \u20103\u03b2"],"prefix":"10.1002","volume":"39","author":[{"given":"Juanlan","family":"Xiao","sequence":"first","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Translational Cancer Research of Chinese Medicines, Joint International Research Laboratory of Translational Cancer Research of Chinese Medicines, International Institute for Translational Chinese Medicine, School of Pharmaceutical Sciences Guangzhou University of Chinese Medicine  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Wu","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Translational Cancer Research of Chinese Medicines, Joint International Research Laboratory of Translational Cancer Research of Chinese Medicines, International Institute for Translational Chinese Medicine, School of Pharmaceutical Sciences Guangzhou University of Chinese Medicine  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lili","family":"Wang","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Translational Cancer Research of Chinese Medicines, Joint International Research Laboratory of Translational Cancer Research of Chinese Medicines, International Institute for Translational Chinese Medicine, School of Pharmaceutical Sciences Guangzhou University of Chinese Medicine  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianmin","family":"Luo","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Translational Cancer Research of Chinese Medicines, Joint International Research Laboratory of Translational Cancer Research of Chinese Medicines, International Institute for Translational Chinese Medicine, School of Pharmaceutical Sciences Guangzhou University of Chinese Medicine  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Wang","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Translational Cancer Research of Chinese Medicines, Joint International Research Laboratory of Translational Cancer Research of Chinese Medicines, International Institute for Translational Chinese Medicine, School of Pharmaceutical Sciences Guangzhou University of Chinese Medicine  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1105-0495","authenticated-orcid":false,"given":"Yuanyuan","family":"Cheng","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Translational Cancer Research of Chinese Medicines, Joint International Research Laboratory of Translational Cancer Research of Chinese Medicines, International Institute for Translational Chinese Medicine, School of Pharmaceutical Sciences Guangzhou University of Chinese Medicine  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Translational Cancer Research of Chinese Medicines, Joint International Research Laboratory of Translational 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