{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T16:16:28Z","timestamp":1790612188223,"version":"4.1.0"},"reference-count":37,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2022,9,1]],"date-time":"2022-09-01T00:00:00Z","timestamp":1661990400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2022,9,1]],"date-time":"2022-09-01T00:00:00Z","timestamp":1661990400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2022,9,1]],"date-time":"2022-09-01T00:00:00Z","timestamp":1661990400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2022,9,1]],"date-time":"2022-09-01T00:00:00Z","timestamp":1661990400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2022,9,1]],"date-time":"2022-09-01T00:00:00Z","timestamp":1661990400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2022,9,1]],"date-time":"2022-09-01T00:00:00Z","timestamp":1661990400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2022,9,1]],"date-time":"2022-09-01T00:00:00Z","timestamp":1661990400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/501100006469","name":"Fundo para o Desenvolvimento das Ci\u00eancias e da Tecnologia","doi-asserted-by":"publisher","award":["0058\/2020\/A2"],"award-info":[{"award-number":["0058\/2020\/A2"]}],"id":[{"id":"10.13039\/501100006469","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011322","name":"Macau University of Science and Technology Foundation","doi-asserted-by":"publisher","award":["001\/2020\/ALC"],"award-info":[{"award-number":["001\/2020\/ALC"]}],"id":[{"id":"10.13039\/501100011322","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011322","name":"Macau University of Science and Technology Foundation","doi-asserted-by":"publisher","award":["FRG-20-003-SKL"],"award-info":[{"award-number":["FRG-20-003-SKL"]}],"id":[{"id":"10.13039\/501100011322","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Phytomedicine"],"published-print":{"date-parts":[[2022,9]]},"DOI":"10.1016\/j.phymed.2022.154140","type":"journal-article","created":{"date-parts":[[2022,5,12]],"date-time":"2022-05-12T01:51:12Z","timestamp":1652320272000},"page":"154140","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":33,"special_numbering":"C","title":["Chelerythrine ameliorates rheumatoid arthritis by modulating the AMPK\/mTOR\/ULK-1 signaling pathway"],"prefix":"10.1016","volume":"104","author":[{"given":"Jun","family":"Cai","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu-Chen","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ren-Jie","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li-Min","family":"Pu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ke-Yuan","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9554-0899","authenticated-orcid":false,"given":"Ali Adnan","family":"Nasim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elaine Lai-Han","family":"Leung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xing-Xing","family":"Fan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.phymed.2022.154140_bib0001","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1080\/1744666X.2017.1351297","article-title":"Update of sarilumb to treat rheumatoid arthritis based on randomized clinical trials: a systematic review","volume":"13","author":"Aly","year":"2017","journal-title":"Expert Rev. Clin. Immunol."},{"key":"10.1016\/j.phymed.2022.154140_bib0002","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1111\/j.0105-2896.2009.00859.x","article-title":"Fibroblast-like synoviocytes: key effector cells in rheumatoid arthritis","volume":"233","author":"Bartok","year":"2010","journal-title":"Immunol. Rev."},{"key":"10.1016\/j.phymed.2022.154140_bib0003","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1038\/nrrheum.2012.190","article-title":"Duality of fibroblast-like synoviocytes in RA: passive responders and imprinted aggressors","volume":"9","author":"Bottini","year":"2013","journal-title":"Nat. Rev. Rheumatol."},{"key":"10.1016\/j.phymed.2022.154140_bib0004","doi-asserted-by":"crossref","first-page":"2338","DOI":"10.1016\/S0140-6736(17)31491-5","article-title":"Novel treatment strategies in rheumatoid arthritis","volume":"389","author":"Burmester","year":"2017","journal-title":"Lancet"},{"key":"10.1016\/j.phymed.2022.154140_bib0005","doi-asserted-by":"crossref","first-page":"720","DOI":"10.1038\/nrrheum.2014.127","article-title":"IL-6 biology: implications for clinical targeting in rheumatic disease","volume":"10","author":"Calabrese","year":"2014","journal-title":"Nat. Rev. Rheumatol."},{"key":"10.1016\/j.phymed.2022.154140_bib0006","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s10753-020-01324-8","article-title":"Focus on the Multimodal Role of Autophagy in Rheumatoid Arthritis","volume":"44","author":"Chadha","year":"2021","journal-title":"Inflammation"},{"key":"10.1016\/j.phymed.2022.154140_bib0007","doi-asserted-by":"crossref","first-page":"3917","DOI":"10.3892\/ol.2016.4520","article-title":"Chelerythrine chloride induces apoptosis in renal cancer HEK-293 and SW-839 cell lines","volume":"11","author":"Chen","year":"2016","journal-title":"Oncol. Lett."},{"key":"10.1016\/j.phymed.2022.154140_bib0008","article-title":"Metformin induces apoptosis and inhibits migration by activating the AMPK\/p53 axis and suppressing PI3K\/AKT signaling in human cervical cancer cells","volume":"23","author":"Chen","year":"2021","journal-title":"Mol. Med. Rep."},{"key":"10.1016\/j.phymed.2022.154140_bib0009","doi-asserted-by":"crossref","first-page":"1209","DOI":"10.1016\/j.biopha.2018.03.142","article-title":"Effects of Artesunate on chondrocyte proliferation, apoptosis and autophagy through the PI3K\/AKT\/mTOR signaling pathway in rat models with rheumatoid arthritis","volume":"102","author":"Feng","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"10.1016\/j.phymed.2022.154140_bib0010","doi-asserted-by":"crossref","first-page":"3399","DOI":"10.1080\/15384101.2020.1859197","article-title":"Coronavirus disease 2019 (COVID-19), human erythrocytes and the PKC-alpha\/-beta inhibitor chelerythrine -possible therapeutic implication","volume":"19","author":"Ghashghaeinia","year":"2020","journal-title":"Cell Cycle"},{"key":"10.1016\/j.phymed.2022.154140_bib0011","first-page":"3228","article-title":"Effect of Huangqin Qingre Chubi Capsules containing serum on oxidative stress and protein expression of AMPK and FoxO3a in rheumatoid arthritis patients","volume":"45","author":"Guo","year":"2020","journal-title":"Zhongguo. Zhong. Yao. Za. Zhi."},{"key":"10.1016\/j.phymed.2022.154140_bib0012","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1038\/s41413-018-0016-9","article-title":"Rheumatoid arthritis: pathological mechanisms and modern pharmacologic therapies","volume":"6","author":"Guo","year":"2018","journal-title":"Bone Res."},{"key":"10.1016\/j.phymed.2022.154140_bib0013","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1111\/jcmm.14295","article-title":"Chelerythrine induces apoptosis via ROS-mediated endoplasmic reticulum stress and STAT3 pathways in human renal cell carcinoma","volume":"24","author":"He","year":"2020","journal-title":"J. Cell. Mol. Med."},{"key":"10.1016\/j.phymed.2022.154140_bib0014","doi-asserted-by":"crossref","DOI":"10.1016\/j.lfs.2020.117734","article-title":"Role of autophagy in the pathogenesis of rheumatoid arthritis: latest evidence and therapeutic approaches","volume":"254","author":"Karami","year":"2020","journal-title":"Life Sci."},{"key":"10.1016\/j.phymed.2022.154140_bib0015","doi-asserted-by":"crossref","first-page":"e2565","DOI":"10.1038\/cddis.2016.490","article-title":"IL-17-mediated mitochondrial dysfunction impairs apoptosis in rheumatoid arthritis synovial fibroblasts through activation of autophagy","volume":"8","author":"Kim","year":"2017","journal-title":"Cell Death Dis."},{"key":"10.1016\/j.phymed.2022.154140_bib0016","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1038\/ncb2152","article-title":"AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1","volume":"13","author":"Kim","year":"2011","journal-title":"Nat. Cell Biol."},{"key":"10.1016\/j.phymed.2022.154140_bib0017","doi-asserted-by":"crossref","first-page":"693","DOI":"10.4103\/0973-1482.126485","article-title":"A benzophenanthridine alkaloid, chelerythrine induces apoptosis in vitro in a Dalton's lymphoma","volume":"9","author":"Kumar","year":"2013","journal-title":"J. Cancer Res. Ther."},{"key":"10.1016\/j.phymed.2022.154140_bib0018","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1038\/nature09782","article-title":"Autophagy in immunity and inflammation","volume":"469","author":"Levine","year":"2011","journal-title":"Nature"},{"key":"10.1016\/j.phymed.2022.154140_bib0019","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1007\/978-981-15-0602-4_4","article-title":"AMPK and Autophagy","volume":"1206","author":"Li","year":"2019","journal-title":"Adv. Exp. Med. Biol."},{"key":"10.1016\/j.phymed.2022.154140_bib0020","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/j.jep.2015.10.010","article-title":"The treatment of rheumatoid arthritis using Chinese medicinal plants: from pharmacology to potential molecular mechanisms","volume":"176","author":"L\u00fc","year":"2015","journal-title":"J. Ethnopharmacol."},{"key":"10.1016\/j.phymed.2022.154140_bib0021","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1097\/BOR.0000000000000496","article-title":"Recent advances in the treatment of rheumatoid arthritis","volume":"30","author":"Mahajan","year":"2018","journal-title":"Curr. Opin. Rheumatol."},{"key":"10.1016\/j.phymed.2022.154140_bib0022","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.phymed.2018.09.004","article-title":"Cinnamaldehyde and eugenol attenuates collagen induced arthritis via reduction of free radicals and pro-inflammatory cytokines","volume":"53","author":"Mateen","year":"2019","journal-title":"Phytomedicine"},{"key":"10.1016\/j.phymed.2022.154140_bib0023","doi-asserted-by":"crossref","first-page":"1564","DOI":"10.1056\/NEJMra2022774","article-title":"Autophagy in Human Diseases","volume":"383","author":"Mizushima","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"10.1016\/j.phymed.2022.154140_bib0024","doi-asserted-by":"crossref","first-page":"890","DOI":"10.1016\/j.phymed.2012.04.001","article-title":"Investigation of sanguinarine and chelerythrine effects on LPS-induced inflammatory gene expression in THP-1 cell line","volume":"19","author":"P\u011bn\u010d\u00edkov\u00e1","year":"2012","journal-title":"Phytomedicine"},{"key":"10.1016\/j.phymed.2022.154140_bib0025","doi-asserted-by":"crossref","first-page":"6353","DOI":"10.1007\/s11033-019-05078-x","article-title":"The impaired gene expression of adenosine monophosphate-activated kinase (AMPK), a key metabolic enzyme in leukocytes of newly diagnosed rheumatoid arthritis patients","volume":"46","author":"Samimi","year":"2019","journal-title":"Mol. Biol. Rep."},{"key":"10.1016\/j.phymed.2022.154140_bib0026","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1038\/nrc2676","article-title":"The LKB1-AMPK pathway: metabolism and growth control in tumour suppression","volume":"9","author":"Shackelford","year":"2009","journal-title":"Nat. Rev. Cancer"},{"key":"10.1016\/j.phymed.2022.154140_bib0027","first-page":"1","article-title":"2015 American College of Rheumatology guideline for the treatment of rheumatoid arthritis","volume":"68","author":"Singh","year":"2016","journal-title":"Rheumatology"},{"key":"10.1016\/j.phymed.2022.154140_bib0028","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1080\/13543784.2017.1276562","article-title":"Glucocorticoid-targeted therapies for the treatment of rheumatoid arthritis","volume":"26","author":"Strehl","year":"2017","journal-title":"Expert Opin. Investig. Drugs"},{"key":"10.1016\/j.phymed.2022.154140_bib0029","doi-asserted-by":"crossref","first-page":"1577","DOI":"10.3389\/fimmu.2018.01577","article-title":"Autophagy and Rheumatoid Arthritis: current Knowledges and Future Perspectives","volume":"9","author":"Vomero","year":"2018","journal-title":"Front. Immunol."},{"key":"10.1016\/j.phymed.2022.154140_bib0030","doi-asserted-by":"crossref","first-page":"2593","DOI":"10.2147\/OTT.S157707","article-title":"Chelerythrine induced cell death through ROS-dependent ER stress in human prostate cancer cells","volume":"11","author":"Wu","year":"2018","journal-title":"Onco. Targets Ther."},{"key":"10.1016\/j.phymed.2022.154140_bib0031","doi-asserted-by":"crossref","first-page":"1829","DOI":"10.1006\/jmcc.2001.1446","article-title":"Chelerythrine rapidly induces apoptosis through generation of reactive oxygen species in cardiac myocytes","volume":"33","author":"Yamamoto","year":"2001","journal-title":"J. Mol. Cell. Cardiol."},{"key":"10.1016\/j.phymed.2022.154140_bib0032","doi-asserted-by":"crossref","first-page":"6396","DOI":"10.1158\/1078-0432.CCR-07-5113","article-title":"Activation of the RAF\/mitogen-activated protein\/extracellular signal-regulated kinase kinase\/extracellular signal-regulated kinase pathway mediates apoptosis induced by chelerythrine in osteosarcoma","volume":"14","author":"Yang","year":"2008","journal-title":"Clin. Cancer Res.: Off. J. Am. Assoc. Cancer Res."},{"key":"10.1016\/j.phymed.2022.154140_bib0033","doi-asserted-by":"crossref","DOI":"10.1016\/j.tiv.2020.104965","article-title":"Chelerythrine hydrochloride inhibits proliferation and induces mitochondrial apoptosis in cervical cancer cells via PI3K\/BAD signaling pathway","volume":"68","author":"Yang","year":"2020","journal-title":"Toxicol. in Vitro"},{"key":"10.1016\/j.phymed.2022.154140_bib0034","doi-asserted-by":"crossref","first-page":"1512","DOI":"10.3389\/fimmu.2018.01512","article-title":"The therapeutic and pathogenic role of autophagy in autoimmune diseases","volume":"9","author":"Yin","year":"2018","journal-title":"Front. Immunol."},{"key":"10.1016\/j.phymed.2022.154140_bib0035","doi-asserted-by":"crossref","first-page":"2070","DOI":"10.1039\/C7FO01748K","article-title":"Apoptosis effects of imperatorin on synoviocytes in rheumatoid arthritis through mitochondrial\/caspase-mediated pathways","volume":"9","author":"Zhai","year":"2018","journal-title":"Food Funct."},{"key":"10.1016\/j.phymed.2022.154140_bib0036","doi-asserted-by":"crossref","first-page":"2856","DOI":"10.1021\/acs.jafc.9b00185","article-title":"Liquiritin from Glycyrrhiza uralensis Attenuating Rheumatoid Arthritis via Reducing Inflammation, Suppressing Angiogenesis, and Inhibiting MAPK Signaling Pathway","volume":"67","author":"Zhai","year":"2019","journal-title":"J. Agric. Food Chem."},{"key":"10.1016\/j.phymed.2022.154140_bib0037","doi-asserted-by":"crossref","first-page":"6073","DOI":"10.1021\/acs.jafc.8b02241","article-title":"Salicin from Alangium chinense Ameliorates Rheumatoid Arthritis by Modulating the Nrf2-HO-1-ROS Pathways","volume":"66","author":"Zhai","year":"2018","journal-title":"J. Agric. Food Chem."}],"container-title":["Phytomedicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0944711322002173?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0944711322002173?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T22:01:02Z","timestamp":1789768862000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0944711322002173"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9]]},"references-count":37,"alternative-id":["S0944711322002173"],"URL":"https:\/\/doi.org\/10.1016\/j.phymed.2022.154140","relation":{},"ISSN":["0944-7113"],"issn-type":[{"value":"0944-7113","type":"print"}],"subject":[],"published":{"date-parts":[[2022,9]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Chelerythrine ameliorates rheumatoid arthritis by modulating the AMPK\/mTOR\/ULK-1 signaling pathway","name":"articletitle","label":"Article Title"},{"value":"Phytomedicine","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.phymed.2022.154140","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2022 Elsevier GmbH. All rights reserved.","name":"copyright","label":"Copyright"}],"article-number":"154140"}}