{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T09:41:33Z","timestamp":1792057293811,"version":"4.4.0"},"reference-count":41,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T00:00:00Z","timestamp":1759795200000},"content-version":"vor","delay-in-days":6,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81673134"],"award-info":[{"award-number":["81673134"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82271474"],"award-info":[{"award-number":["82271474"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82301630"],"award-info":[{"award-number":["82301630"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82071221"],"award-info":[{"award-number":["82071221"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004608","name":"Natural Science Foundation of Jiangsu Province","doi-asserted-by":"publisher","award":["BK20230180"],"award-info":[{"award-number":["BK20230180"]}],"id":[{"id":"10.13039\/501100004608","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012151","name":"Sanming Project of Medicine in Shenzhen","doi-asserted-by":"publisher","award":["SZSM202211010"],"award-info":[{"award-number":["SZSM202211010"]}],"id":[{"id":"10.13039\/501100012151","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2025,10]]},"abstract":"ABSTRACT<\/jats:title>\n \n Background<\/jats:title>\n Duchenne muscular dystrophy (DMD) is a genetic disorder characterized by progressive muscle weakness, with inflammation and fibrosis contributing to its pathogenesis. Despite advancements in genetic disease\u2010modifying treatment, there is currently no effective pharmacological treatment for DMD.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n New compound ARC\u201018, a derivative of Arctigenin known for its anti\u2010inflammatory activity, was designed and synthesized in our lab and administered prophylactically to 2\u2010month\u2010old mdx mice for 60\u2009days. The motor performance was investigated by rotarod test, climbing\u2010pole test, grip strength test, hanging endurance test, treadmill endurance test and gait analysis. Afterwards, molecular biological experiments, including proteomics, immunohistochemistry, immunofluorescence, western blots, gene transfection and immunoprecipitation, were employed to investigate the molecular mechanism of ARC\u201018 in the treatment of mdx.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n ARC\u201018 significantly ameliorated the motor performance of DMD mice (rotating time +65.9%,\n p<\/jats:italic>\n < 0.01; hanging time +59.7%,\n p<\/jats:italic>\n < 0.05; grip strength +32.1%,\n p<\/jats:italic>\n < 0.0001; climbing time \u221229.0%,\n p<\/jats:italic>\n < 0.0001; numbers of electric shocks \u221269.3%,\n p<\/jats:italic>\n < 0.01) by up\u2010regulating the expression of dystrophin\u2010associated proteins (dystrophin,\n p<\/jats:italic>\n \u2009<\u20090.01; \u03b1\u2010dystroglycan,\n p<\/jats:italic>\n \u2009<\u20090.01) and down\u2010regulating the expression of muscle satellite\/stem cell proteins (Pax7,\n p<\/jats:italic>\n \u2009<\u20090.05; Myod,\n p<\/jats:italic>\n \u2009<\u20090.05; Myog,\n p<\/jats:italic>\n \u2009<\u20090.05; \u03b1\u2010SMA,\n p<\/jats:italic>\n \u2009<\u20090.01; fibronectin,\n p<\/jats:italic>\n \u2009<\u20090.001; collagen I,\n p<\/jats:italic>\n \u2009<\u20090.05). ARC\u201018 prevented the progression of muscle fibrosis, reduced inflammatory factors transforming growth factor (TGF) \u03b21 (\n p<\/jats:italic>\n \u2009<\u20090.05), IL\u20101\u03b2 (\n p<\/jats:italic>\n \u2009<\u20090.05) and TNF\u2010\u03b1 (\n p<\/jats:italic>\n \u2009<\u20090.05) levels, and promoted the structural integrity of gastrocnemius and triceps muscles. Proteomics analysis demonstrated that ARC\u201018 treatment reversed the protein expression pattern of DMD model mice, with ATP\u2010citrate synthase (ACLY) enriched in the TCA cycle pathway, showing a significant correlation with DMD expression levels (\n R<\/jats:italic>\n \u2009=\u2009\u22120.72,\n p<\/jats:italic>\n \u2009=\u20090.00031). Further investigations revealed that ARC\u201018 directly bound with ACLY (EC\n 50<\/jats:sub>\n \u2009=\u2009120.2\u2009nM) to promote its degradation by the proteasome system and suppressed the ACLY\u2010mediated acetylation of Smad2\/3 (\n p<\/jats:italic>\n \u2009<\u20090.01) to reduce its nuclear localization (\n p<\/jats:italic>\n \u2009<\u20090.05) to inhibit fibrosis.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n Our study indicated that oral ARC\u201018 treatment decelerated the progression of neuromuscular disease in a reliable DMD animal model, suggesting its potential as a promising drug for DMD.<\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/jcsm.70081","type":"journal-article","created":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T07:00:27Z","timestamp":1759820427000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["ARC\u201018 Improved Motor Performance Through Inhibiting ACLY\u2010Mediated Smad2\/3 Acetylation in a Model of Duchenne Muscular Dystrophy"],"prefix":"10.1002","volume":"16","author":[{"given":"Chongyang","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Pathophysiology, School of Basic Medicine, Key Laboratory of Ministry of Education of China and Hubei Province for Neurological Disorders Tongji Medical College, Huazhong University of Science and Technology Wuhan China"},{"name":"National Health Commission Key Laboratory of Nuclear Medicine, Jiangsu Key Laboratory of Molecular Nuclear Medicine Jiangsu Institute of Nuclear Medicine Wuxi China"},{"name":"Shenzhen Key Laboratory of Modern Toxicology, Shenzhen Medical Key Discipline of Health Toxicology (2020\u20132024) Shenzhen Center for Disease Control and Prevention Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bingge","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology, School of Basic Medicine, Key Laboratory of Ministry of Education of China and Hubei Province for Neurological Disorders Tongji Medical College, Huazhong University of Science and Technology Wuhan China"},{"name":"Shenzhen Key Laboratory of Modern Toxicology, Shenzhen Medical Key Discipline of Health Toxicology (2020\u20132024) Shenzhen Center for Disease Control and Prevention Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Yang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Biotherapy and Cancer Center, West China Hospital Sichuan University and Collaborative Innovation Center of Biotherapy Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Wang","sequence":"additional","affiliation":[{"name":"Shenzhen Key Laboratory of Modern Toxicology, Shenzhen Medical Key Discipline of Health Toxicology (2020\u20132024) Shenzhen Center for Disease Control and Prevention Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ye","family":"He","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology, School of Basic Medicine, Key Laboratory of Ministry of Education of China and Hubei Province for Neurological Disorders Tongji Medical College, Huazhong University of Science and Technology Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haitao","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology, School of Basic Medicine, Key Laboratory of Ministry of Education of China and Hubei Province for Neurological Disorders Tongji Medical College, Huazhong University of Science and Technology Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianjun","family":"Liu","sequence":"additional","affiliation":[{"name":"Shenzhen Key Laboratory of Modern Toxicology, Shenzhen Medical Key Discipline of Health Toxicology (2020\u20132024) Shenzhen Center for Disease Control and Prevention Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongmei","family":"Xie","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Biotherapy and Cancer Center, West China Hospital Sichuan University and Collaborative Innovation Center of Biotherapy Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xifei","family":"Yang","sequence":"additional","affiliation":[{"name":"Shenzhen Key Laboratory of Modern Toxicology, Shenzhen Medical Key Discipline of Health Toxicology (2020\u20132024) Shenzhen Center for Disease Control and Prevention Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gong\u2010Ping","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology, School of Basic Medicine, Key Laboratory of Ministry of Education of China and Hubei Province for Neurological Disorders Tongji Medical College, Huazhong University of Science and Technology Wuhan China"},{"name":"Co\u2010Innovation Center of Neuroregeneration Nantong University Nantong Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,10,7]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-021-00248-3"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2018.10.010"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2023.1183101"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2008.23"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/2044-5040-4-7"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-06068-6"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00132.2011"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.135703"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.12414"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2023.154647"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2017.09.117"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2020.11539"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20061328"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2021.174419"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1080\/14756366.2022.2115035"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.abb0319"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-022-00998-w"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2022.110939"},{"key":"e_1_2_10_20_1","article-title":"Assessing 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