{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T17:43:18Z","timestamp":1777398198025,"version":"3.51.4"},"reference-count":44,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2024,3,1]],"date-time":"2024-03-01T00:00:00Z","timestamp":1709251200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2024,3,1]],"date-time":"2024-03-01T00:00:00Z","timestamp":1709251200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2024,3,1]],"date-time":"2024-03-01T00:00:00Z","timestamp":1709251200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2024,3,1]],"date-time":"2024-03-01T00:00:00Z","timestamp":1709251200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2024,3,1]],"date-time":"2024-03-01T00:00:00Z","timestamp":1709251200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2024,3,1]],"date-time":"2024-03-01T00:00:00Z","timestamp":1709251200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2024,3,1]],"date-time":"2024-03-01T00:00:00Z","timestamp":1709251200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81973449"],"award-info":[{"award-number":["81973449"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Phytomedicine"],"published-print":{"date-parts":[[2024,3]]},"DOI":"10.1016\/j.phymed.2024.155356","type":"journal-article","created":{"date-parts":[[2024,1,14]],"date-time":"2024-01-14T15:54:49Z","timestamp":1705247689000},"page":"155356","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":6,"special_numbering":"C","title":["Catalpolaglycone disrupts mitochondrial thermogenesis by specifically binding to a conserved lysine residue of UCP2 on the proton leak tunnel"],"prefix":"10.1016","volume":"125","author":[{"given":"Fukui","family":"Shen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5451-4101","authenticated-orcid":false,"given":"Wen","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guoqing","family":"Luan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiamin","family":"Peng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhenqiang","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4887-7816","authenticated-orcid":false,"given":"Jie","family":"Gao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6080-8322","authenticated-orcid":false,"given":"Yuanyuan","family":"Hou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gang","family":"Bai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"key":"10.1016\/j.phymed.2024.155356_bib0001","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1517\/17460441.2016.1115478","article-title":"New drug design with covalent modifiers","volume":"11","author":"Adeniyi","year":"2016","journal-title":"Expert. Opin. Drug. Discov."},{"key":"10.1016\/j.phymed.2024.155356_bib0002","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1007\/s10930-020-09884-2","article-title":"Covalent versus non-covalent enzyme inhibition: which route should we take? A justification of the good and bad from molecular modelling perspective","volume":"39","author":"Aljoundi","year":"2020","journal-title":"Protein J."},{"key":"10.1016\/j.phymed.2024.155356_bib0003","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1134\/S1607672908060021","article-title":"The role of UCP2 and ADP\/ATP antiporter in superoxide radical-induced uncoupling in kidney mitochondria","volume":"423","author":"Amerkhanov","year":"2008","journal-title":"Dokl. Biochem. Biophys."},{"key":"10.1016\/j.phymed.2024.155356_bib0004","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1146\/annurev-physiol-021119-034405","article-title":"Mitochondrial H(+) leak and thermogenesis","volume":"84","author":"Bertholet","year":"2022","journal-title":"Annu. Rev. Physiol."},{"key":"10.1016\/j.phymed.2024.155356_bib0005","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1016\/j.bj.2022.05.002","article-title":"Targeting mitochondrial bioenergetics as a promising therapeutic strategy in metabolic and neurodegenerative diseases","volume":"45","author":"Bhatti","year":"2022","journal-title":"Biomed. J."},{"key":"10.1016\/j.phymed.2024.155356_bib0006","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/j.cardiores.2006.07.019","article-title":"Mitochondrial uncoupling, with low concentration FCCP, induces ROS-dependent cardioprotection independent of KATP channel activation","volume":"72","author":"Brennan","year":"2006","journal-title":"Cardiovasc. Res."},{"key":"10.1016\/j.phymed.2024.155356_bib0007","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1016\/j.trecan.2017.10.006","article-title":"Mitochondria, bioenergetics and apoptosis in cancer","volume":"3","author":"Burke","year":"2017","journal-title":"Trends Cancer"},{"key":"10.1016\/j.phymed.2024.155356_bib0008","doi-asserted-by":"crossref","first-page":"292","DOI":"10.2174\/1389557518666181026091449","article-title":"Occurrence and biological activities of phenylpropionyl iridoids","volume":"19","author":"Cao","year":"2019","journal-title":"Mini Rev. Med. Chem."},{"key":"10.1016\/j.phymed.2024.155356_bib0009","doi-asserted-by":"crossref","first-page":"3407","DOI":"10.1038\/s41598-019-39939-z","article-title":"Merits and pitfalls of conventional and covalent docking in identifying new hydroxyl aryl aldehyde like compounds as human IRE1 inhibitors","volume":"9","author":"Carlesso","year":"2019","journal-title":"Sci. Rep."},{"key":"10.1016\/j.phymed.2024.155356_bib0010","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pcbi.1002708","article-title":"CAVER 3.0: a tool for the analysis of transport pathways in dynamic protein structures","volume":"8","author":"Chovancova","year":"2012","journal-title":"PLoS Comput. Biol."},{"key":"10.1016\/j.phymed.2024.155356_bib0011","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1007\/s11033-022-08055-z","article-title":"Mitochondrial uncoupling protein 2 (UCP2) gene polymorphism - 866G\/A in the promoter region is associated with type 2 diabetes mellitus among Kashmiri population of Northern India","volume":"50","author":"Din","year":"2023","journal-title":"Mol. Biol. Rep."},{"key":"10.1016\/j.phymed.2024.155356_bib0012","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1080\/15216540211468","article-title":"Structural basis of perturbed pKa values of catalytic groups in enzyme active sites","volume":"53","author":"Harris","year":"2002","journal-title":"IUBMB Life"},{"key":"10.1016\/j.phymed.2024.155356_bib0013","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1007\/s10753-018-0873-9","article-title":"Catalpol inhibits homocysteine-induced oxidation and inflammation via inhibiting Nox4\/NF-kappaB and GRP78\/PERK pathways in human aorta endothelial cells","volume":"42","author":"Hu","year":"2019","journal-title":". Inflammation"},{"key":"10.1016\/j.phymed.2024.155356_bib0014","doi-asserted-by":"crossref","first-page":"76","DOI":"10.3748\/wjg.v23.i1.76","article-title":"miRNA-133a-UCP2 pathway regulates inflammatory bowel disease progress by influencing inflammation, oxidative stress and energy metabolism","volume":"23","author":"Jin","year":"2017","journal-title":"World J. Gastroenterol."},{"key":"10.1016\/j.phymed.2024.155356_bib0015","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1016\/j.redox.2017.07.012","article-title":"Upregulation of UCP2 in beta-cells confers partial protection against both oxidative stress and glucotoxicity","volume":"13","author":"Li","year":"2017","journal-title":"Redox. Biol."},{"key":"10.1016\/j.phymed.2024.155356_bib0016","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/j.ijdevneu.2008.01.006","article-title":"Catalpol protects primary cultured astrocytes from in vitro ischemia-induced damage","volume":"26","author":"Li","year":"2008","journal-title":"Int. J. Dev. Neurosci."},{"key":"10.1016\/j.phymed.2024.155356_bib0017","doi-asserted-by":"crossref","DOI":"10.1016\/j.taap.2019.114624","article-title":"Role of intestinal microbiota-mediated genipin dialdehyde intermediate formation in geniposide-induced hepatotoxicity in rats","volume":"377","author":"Li","year":"2019","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"10.1016\/j.phymed.2024.155356_bib0018","doi-asserted-by":"crossref","DOI":"10.1155\/2019\/8743257","article-title":"Mitochondrial F-ATP synthase and its transition into an energy-dissipating molecular machine","volume":"2019","author":"Lippe","year":"2019","journal-title":"Oxid. Med. Cell. Longev."},{"key":"10.1016\/j.phymed.2024.155356_bib0019","doi-asserted-by":"crossref","DOI":"10.1002\/mnfr.202100963","article-title":"Cinnamaldehyde regulates the generation of gamma-aminobutyric acid to exert sedation via irreversible inhibition of ENO1 in the cerebellar granular layer","volume":"66","author":"Ma","year":"2022","journal-title":"Mol. Nutr. Food Res."},{"key":"10.1016\/j.phymed.2024.155356_bib0020","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1038\/s41401-020-00534-y","article-title":"Ursolic acid reduces hepatocellular apoptosis and alleviates alcohol-induced liver injury via irreversible inhibition of CASP3 in vivo","volume":"42","author":"Ma","year":"2021","journal-title":"Acta Pharmacol. Sin."},{"key":"10.1016\/j.phymed.2024.155356_bib0021","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1039\/C6TX00410E","article-title":"The UCP2-related mitochondrial pathway participates in rhein-induced apoptosis in HK-2 cells","volume":"6","author":"Mao","year":"2017","journal-title":"Toxicol. Res. (Camb)"},{"key":"10.1016\/j.phymed.2024.155356_bib0022","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/S0008-6363(00)00069-9","article-title":"Dinitrophenol, cyclosporin A, and trimetazidine modulate preconditioning in the isolated rat heart: support for a mitochondrial role in cardioprotection","volume":"47","author":"Minners","year":"2000","journal-title":"Cardiovasc. Res."},{"key":"10.1016\/j.phymed.2024.155356_bib0023","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1038\/sj.embor.7400532","article-title":"Uncoupling proteins: current status and therapeutic prospects","volume":"6","author":"Nedergaard","year":"2005","journal-title":"EMBO Rep."},{"key":"10.1016\/j.phymed.2024.155356_bib0024","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1096\/fasebj.11.10.9271366","article-title":"A role for uncoupling protein-2 as a regulator of mitochondrial hydrogen peroxide generation","volume":"11","author":"Negre-Salvayre","year":"1997","journal-title":"FASEB J."},{"key":"10.1016\/j.phymed.2024.155356_bib0025","doi-asserted-by":"crossref","first-page":"15225","DOI":"10.1074\/jbc.M117.802702","article-title":"A plant\/fungal-type phosphoenolpyruvate carboxykinase located in the parasite mitochondrion ensures glucose-independent survival of Toxoplasma gondii","volume":"292","author":"Nitzsche","year":"2017","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.phymed.2024.155356_bib0026","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1021\/ct100578z","article-title":"PROPKA3: consistent treatment of internal and surface residues in empirical pKa predictions","volume":"7","author":"Olsson","year":"2011","journal-title":"J. Chem. Theory Comput."},{"key":"10.1016\/j.phymed.2024.155356_bib0027","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1093\/ecam\/nem129","article-title":"Inhibitory potencies of several iridoids on cyclooxygenase-1, cyclooxygnase-2 enzymes activities, tumor necrosis factor-alpha and nitric oxide production in vitro","volume":"7","author":"Park","year":"2010","journal-title":"Evid. Based Complement. Alternat. Med."},{"key":"10.1016\/j.phymed.2024.155356_bib0028","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1109\/TCBB.2015.2459680","article-title":"CAVER: algorithms for analyzing dynamics of tunnels in macromolecules","volume":"13","author":"Pavelka","year":"2016","journal-title":"IEEE\/ACM Trans. Comput. Biol. Bioinform."},{"key":"10.1016\/j.phymed.2024.155356_bib0029","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1007\/s10858-014-9862-y","article-title":"pH-dependent random coil (1)H, (13)C, and (15)N chemical shifts of the ionizable amino acids: a guide for protein pK a measurements","volume":"60","author":"Platzer","year":"2014","journal-title":"J. Biomol. NMR"},{"key":"10.1016\/j.phymed.2024.155356_bib0030","doi-asserted-by":"crossref","first-page":"16512","DOI":"10.1016\/S0021-9258(18)55330-8","article-title":"Inhibition of venom phospholipases A2 by manoalide and manoalogue. Stoichiometry of incorporation","volume":"266","author":"Reynolds","year":"1991","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.phymed.2024.155356_bib0031","first-page":"24","article-title":"Importance of mitochondria in cardiac pathologies: focus on uncoupling proteins and monoamine oxidases","author":"Schulz","year":"2023","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.phymed.2024.155356_bib0032","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1016\/j.cellsig.2007.10.015","article-title":"Taxol-induced mitochondrial stress in melanoma cells is mediated by activation of c-Jun N-terminal kinase (JNK) and p38 pathways via uncoupling protein 2","volume":"20","author":"Selimovic","year":"2008","journal-title":"Cell. Signal."},{"key":"10.1016\/j.phymed.2024.155356_bib0033","doi-asserted-by":"crossref","first-page":"13417","DOI":"10.1021\/acs.analchem.1c03554","article-title":"Small-molecule fluorogenic probe for the detection of mitochondrial temperature in vivo","volume":"93","author":"Shen","year":"2021","journal-title":"Anal. Chem."},{"key":"10.1016\/j.phymed.2024.155356_bib0034","doi-asserted-by":"crossref","first-page":"1785","DOI":"10.1007\/s00018-009-9183-6","article-title":"Functions of mitochondria: from intracellular power stations to mediators of a senescence program","volume":"66","author":"Skulachev","year":"2009","journal-title":"Cell. Mol. Life Sci."},{"key":"10.1016\/j.phymed.2024.155356_bib0035","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1021\/ct8000014","article-title":"Benchmarking pKa prediction methods for residues in proteins","volume":"4","author":"Stanton","year":"2008","journal-title":"J. Chem. Theory Comput."},{"key":"10.1016\/j.phymed.2024.155356_bib0036","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/j.jchromb.2015.12.007","article-title":"Biotransformation and metabolic profile of catalpol with human intestinal microflora by ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry","volume":"1009-1010","author":"Tao","year":"2016","journal-title":"J. Chromatogr. B Analyt. Technol. Biomed. Life. Sci."},{"key":"10.1016\/j.phymed.2024.155356_bib0037","first-page":"251","article-title":"Modes of action of herbal medicines and plant secondary metabolites","volume":"2","author":"Wink","year":"2015","journal-title":"Medicines (Basel)"},{"key":"10.1016\/j.phymed.2024.155356_bib0038","doi-asserted-by":"crossref","DOI":"10.1016\/j.yexcr.2020.112110","article-title":"UCP2 silencing in glioblastoma reduces cell proliferation and invasiveness by inhibiting p38 MAPK pathway","volume":"394","author":"Wu","year":"2020","journal-title":"Exp. Cell Res."},{"key":"10.1016\/j.phymed.2024.155356_bib0039","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/j.lfs.2018.08.028","article-title":"A new hypoglycemic mechanism of catalpol revealed by enhancing MyoD\/MyoG-mediated myogenesis","volume":"209","author":"Xu","year":"2018","journal-title":"Life Sci."},{"key":"10.1016\/j.phymed.2024.155356_bib0040","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1038\/s41401-019-0345-2","article-title":"The hypoglycemic mechanism of catalpol involves increased AMPK-mediated mitochondrial biogenesis","volume":"41","author":"Xu","year":"2020","journal-title":"Acta Pharmacol. Sin."},{"key":"10.1016\/j.phymed.2024.155356_bib0041","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1016\/j.cmet.2006.04.010","article-title":"Genipin inhibits UCP2-mediated proton leak and acutely reverses obesity- and high glucose-induced beta cell dysfunction in isolated pancreatic islets","volume":"3","author":"Zhang","year":"2006","journal-title":"Cell Metab."},{"key":"10.1016\/j.phymed.2024.155356_bib0042","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1016\/j.bbrc.2007.06.071","article-title":"Uncoupling protein 2 protects testicular germ cells from hyperthermia-induced apoptosis","volume":"360","author":"Zhang","year":"2007","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"10.1016\/j.phymed.2024.155356_bib0043","article-title":"Cinnamaldehyde enhances antimelanoma activity through covalently binding ENO1 and exhibits a promoting effect with dacarbazine","volume":"12","author":"Zhang","year":"2020","journal-title":"Cancers (Basel)"},{"key":"10.1016\/j.phymed.2024.155356_bib0044","doi-asserted-by":"crossref","first-page":"12109","DOI":"10.1038\/ncomms12109","article-title":"MCOLN1 is a ROS sensor in lysosomes that regulates autophagy","volume":"7","author":"Zhang","year":"2016","journal-title":"Nat. Commun."}],"container-title":["Phytomedicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0944711324000217?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0944711324000217?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T18:52:45Z","timestamp":1760554365000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0944711324000217"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3]]},"references-count":44,"alternative-id":["S0944711324000217"],"URL":"https:\/\/doi.org\/10.1016\/j.phymed.2024.155356","relation":{},"ISSN":["0944-7113"],"issn-type":[{"value":"0944-7113","type":"print"}],"subject":[],"published":{"date-parts":[[2024,3]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Catalpolaglycone disrupts mitochondrial thermogenesis by specifically binding to a conserved lysine residue of UCP2 on the proton leak tunnel","name":"articletitle","label":"Article Title"},{"value":"Phytomedicine","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.phymed.2024.155356","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2024 Elsevier GmbH. All rights reserved.","name":"copyright","label":"Copyright"}],"article-number":"155356"}}