{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,30]],"date-time":"2026-05-30T00:02:40Z","timestamp":1780099360456,"version":"3.54.0"},"reference-count":42,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,5,14]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Rheumatoid arthritis (RA) is characterized by severe synovial inflammation and progressive joint destruction. This study evaluated the therapeutic effects of electroacupuncture (EA) in a rat model of RA and explored its potential association with lipoic acid (LA) metabolism. Collagen-induced arthritis (CIA) was established in rats, followed by EA stimulation at ST36 (Zusanli) for 14\u2009d. Hind-paw thickness and arthritis index scores were assessed weekly. On day 28, synovial histopathology was examined by hematoxylin and eosin staining. Serum cytokine levels were measured by ELISA. Synovial tissue metabolomics was performed to identify EA-responsive metabolic pathways, and candidate proteins were validated by Western blotting. Serum copper (Cu2+) levels were also quantified. The results demonstrated that EA alleviated CIA manifestations in an intensity-dependent manner, with low-intensity stimulation (0.5\u2009mA) showing the greatest efficacy. EA reduced joint damage and systemic inflammation, as reflected by increased IL-10 and decreased TNF-\u03b1, IL-6, and IL-17 levels. Metabolomic analysis highlighted alterations in LA metabolism. Protein levels of DLAT and LIAS were elevated in CIA rats and were reduced after EA or methotrexate treatment. Serum Cu2+ levels exhibited a similar trend. In conclusion, low-intensity EA attenuates joint inflammation in CIA rats, potentially through modulation of LA metabolism and associated copper homeostasis, providing new metabolic insights into its anti-inflammatory effects in RA.<\/jats:p>","DOI":"10.1093\/jimmun\/vkag083","type":"journal-article","created":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T23:40:14Z","timestamp":1780098014000},"source":"Crossref","is-referenced-by-count":0,"title":["The role of electroacupuncture in altering lipoic acid metabolism to reduce joint inflammation in rheumatoid arthritis rats"],"prefix":"10.1093","volume":"215","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-1361-7709","authenticated-orcid":false,"given":"Chuchu","family":"Shen","sequence":"first","affiliation":[{"name":"Key Laboratory of Acupuncture and Medicine Research of Ministry of Education, Nanjing University of Chinese Medicine , Nanjing,","place":["China"]},{"name":"Acupuncture and Tuina College, Nanjing University of Chinese Medicine , Nanjing,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuo","family":"Qiu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Acupuncture and Medicine Research of Ministry of Education, Nanjing University of Chinese Medicine , Nanjing,","place":["China"]},{"name":"Acupuncture and Tuina College, Nanjing University of Chinese Medicine , Nanjing,","place":["China"]},{"name":"Department of Acupuncture and Moxibustion, Yangzhou Hospital of Traditional Chinese Medicine , Yangzhou,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin-Xue","family":"Jiang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Acupuncture and Medicine Research of Ministry of Education, Nanjing University of Chinese Medicine , Nanjing,","place":["China"]},{"name":"Acupuncture and Tuina College, Nanjing University of Chinese Medicine , Nanjing,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian-Feng","family":"Lian","sequence":"additional","affiliation":[{"name":"Department of Acupuncture and Moxibustion, HaiAn Hospital of Traditional Chinese Medicine , Nantong,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue-Feng","family":"Xia","sequence":"additional","affiliation":[{"name":"Key Laboratory of Acupuncture and Medicine Research of Ministry of Education, Nanjing University of Chinese Medicine , Nanjing,","place":["China"]},{"name":"Acupuncture and Tuina College, Nanjing University of Chinese Medicine , Nanjing,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sen-Lei","family":"Xu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Acupuncture and Medicine Research of Ministry of Education, Nanjing University of Chinese Medicine , Nanjing,","place":["China"]},{"name":"Acupuncture and Tuina College, Nanjing University of Chinese Medicine , Nanjing,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Lin","sequence":"additional","affiliation":[{"name":"School of Integrative Medicine, Nanjing University of Chinese Medicine , Nanjing,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong-Ru","family":"Zhang","sequence":"additional","affiliation":[{"name":"Acupuncture and Tuina College, Nanjing University of Chinese Medicine , Nanjing,","place":["China"]},{"name":"School of Chinese Medicine, Nanjing University of Chinese Medicine , Nanjing,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,5,28]]},"reference":[{"key":"2026052919400582300_vkag083-B1","doi-asserted-by":"crossref","first-page":"1108","DOI":"10.1002\/art.41752","article-title":"2021 American College of Rheumatology guideline for the treatment of rheumatoid arthritis","volume":"73","author":"Fraenkel","year":"2021","journal-title":"Arthritis Rheumatol"},{"key":"2026052919400582300_vkag083-B2","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1186\/s12955-021-01874-x","article-title":"Impact of socio-demographic and clinical characteristics on functional disability and health-related quality of life in patients with rheumatoid arthritis: a cross-sectional study from Palestine","volume":"19","author":"Al-Jabi","year":"2021","journal-title":"Health Qual Life Outcomes"},{"key":"2026052919400582300_vkag083-B3","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1007\/s00296-018-4021-5","article-title":"Clinical connection between rheumatoid arthritis and liver damage","volume":"38","author":"Radovanovi\u0107-Dini\u0107","year":"2018","journal-title":"Rheumatol Int"},{"key":"2026052919400582300_vkag083-B4","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1186\/s13075-015-0728-9","article-title":"Incidence of malignancy in adult patients with rheumatoid arthritis: a meta-analysis","volume":"17","author":"Simon","year":"2015","journal-title":"Arthritis Res Ther"},{"key":"2026052919400582300_vkag083-B5","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1038\/s41584-023-00969-7","article-title":"Shared inflammatory pathways of rheumatoid arthritis and atherosclerotic cardiovascular disease","volume":"19","author":"Weber","year":"2023","journal-title":"Nat Rev Rheumatol"},{"key":"2026052919400582300_vkag083-B6","doi-asserted-by":"crossref","first-page":"1532","DOI":"10.1136\/annrheumdis-2020-217092","article-title":"Infectious complications of rheumatoid arthritis and psoriatic arthritis during targeted and biological therapies: a viewpoint in 2020","volume":"79","author":"Lortholary","year":"2020","journal-title":"Ann Rheum Dis"},{"key":"2026052919400582300_vkag083-B7","doi-asserted-by":"crossref","first-page":"1463","DOI":"10.1136\/annrheumdis-2019-215920","article-title":"Global, regional, and national burden of rheumatoid arthritis, 1990\u20132017: a systematic analysis for the Global Burden of Disease Study 2017","volume":"78","author":"Safiri","year":"2019","journal-title":"Ann Rheum Dis"},{"key":"2026052919400582300_vkag083-B8","doi-asserted-by":"crossref","first-page":"161","DOI":"10.3390\/cells7100161","article-title":"Pathogenic role of immune cells in rheumatoid arthritis: implications in clinical treatment and biomarker development","volume":"7","author":"Yap","year":"2018","journal-title":"Cells"},{"key":"2026052919400582300_vkag083-B9","doi-asserted-by":"crossref","first-page":"1299","DOI":"10.1002\/art.42507","article-title":"2022 American College of Rheumatology guideline for exercise, rehabilitation, diet, and additional integrative interventions for rheumatoid arthritis","volume":"75","author":"England","year":"2023","journal-title":"Arthritis Rheumatol"},{"key":"2026052919400582300_vkag083-B10","doi-asserted-by":"crossref","first-page":"829409","DOI":"10.3389\/fimmu.2022.829409","article-title":"Comparison of efficacy of acupuncture-related therapy in the treatment of rheumatoid arthritis: a network meta-analysis of randomized controlled trials","volume":"13","author":"Wan","year":"2022","journal-title":"Front Immunol"},{"key":"2026052919400582300_vkag083-B11","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1097\/JCMA.0000000000000659","article-title":"The effects of acupuncture and related techniques on patients with rheumatoid arthritis: a systematic review and meta-analysis","volume":"85","author":"Lu","year":"2022","journal-title":"J Chin Med Assoc"},{"key":"2026052919400582300_vkag083-B12","doi-asserted-by":"crossref","first-page":"8596918","DOI":"10.1155\/2018\/8596918","article-title":"Clinical efficacy of acupuncture on rheumatoid arthritis and associated mechanisms: a systematic review","volume":"2018","author":"Chou","year":"2018","journal-title":"Evid Based Complement Alternat Med"},{"key":"2026052919400582300_vkag083-B13","doi-asserted-by":"crossref","first-page":"1669","DOI":"10.1136\/ard-2022-222871","article-title":"Stage-specific roles of microbial dysbiosis and metabolic disorders in rheumatoid arthritis","volume":"81","author":"Cheng","year":"2022","journal-title":"Ann Rheum Dis"},{"key":"2026052919400582300_vkag083-B14","first-page":"500","article-title":"Progress of research on mechanisms of acupuncture and moxibustion in the treatment of rheumatoid arthritis","volume":"48","author":"Su","year":"2023","journal-title":"Zhen Ci Yan Jiu"},{"key":"2026052919400582300_vkag083-B15","first-page":"e14567","article-title":"Efficacy and safety of electroacupuncture combined with medication for rheumatoid arthritis: a systematic review and meta-analysis","volume":"9","author":"Feng","year":"2023","journal-title":"Heliyon"},{"key":"2026052919400582300_vkag083-B16","doi-asserted-by":"crossref","first-page":"779787","DOI":"10.3389\/fimmu.2021.779787","article-title":"Glycolysis rate-limiting enzymes: novel potential regulators of rheumatoid arthritis pathogenesis","volume":"12","author":"Zuo","year":"2021","journal-title":"Front Immunol"},{"key":"2026052919400582300_vkag083-B17","first-page":"1479","article-title":"Research progress of acupuncture in the treatment of rheumatoid arthritis","volume":"44","author":"Lin","year":"2024","journal-title":"Chin Acupunct Moxibustion"},{"key":"2026052919400582300_vkag083-B18","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1007\/s10545-014-9705-8","article-title":"Lipoic acid biosynthesis defects","volume":"37","author":"Mayr","year":"2014","journal-title":"J Inherit Metab Dis"},{"key":"2026052919400582300_vkag083-B19","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1042\/BST0340217","article-title":"Regulation of the pyruvate dehydrogenase complex","volume":"34","author":"Patel","year":"2006","journal-title":"Biochem Soc Trans"},{"key":"2026052919400582300_vkag083-B20","doi-asserted-by":"crossref","first-page":"1254","DOI":"10.1126\/science.abf0529","article-title":"Copper induces cell death by targeting lipoylated TCA cycle proteins","volume":"375","author":"Tsvetkov","year":"2022","journal-title":"Science"},{"key":"2026052919400582300_vkag083-B21","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1080\/07315724.2014.910740","article-title":"Effects of alpha-lipoic acid supplementation on inflammatory biomarkers and matrix metalloproteinase-3 in rheumatoid arthritis patients: a randomized, double-blind, placebo-controlled trial","volume":"34","author":"Mirtaheri","year":"2015","journal-title":"J Am Coll Nutr"},{"key":"2026052919400582300_vkag083-B22","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1024\/0300-9831\/a000550","article-title":"Oral administration of alpha-lipoic acid did not significantly affect lipid peroxidation and antioxidant biomarkers in rheumatoid arthritis patients: a randomized clinical trial","volume":"89","author":"Kolahi","year":"2019","journal-title":"Int J Vitam Nutr Res"},{"key":"2026052919400582300_vkag083-B23","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1016\/0891-5849(95)00017-R","article-title":"Alpha-lipoic acid as a biological antioxidant","volume":"19","author":"Packer","year":"1995","journal-title":"Free Radic Biol Med"},{"key":"2026052919400582300_vkag083-B24","doi-asserted-by":"crossref","first-page":"e3535","DOI":"10.1002\/jgm.3535","article-title":"Identification of a novel cuproptosis-related gene signature for rheumatoid arthritis: a prospective study","volume":"25","author":"Hu","year":"2023","journal-title":"J Gene Med"},{"key":"2026052919400582300_vkag083-B25","doi-asserted-by":"crossref","first-page":"1204926","DOI":"10.3389\/fendo.2023.1204926","article-title":"Verification of cuproptosis-related diagnostic model associated with immune infiltration in rheumatoid arthritis","volume":"14","author":"Jiang","year":"2023","journal-title":"Front Endocrinol (Lausanne)"},{"key":"2026052919400582300_vkag083-B26","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":"2026052919400582300_vkag083-B27","doi-asserted-by":"crossref","first-page":"9050763","DOI":"10.1155\/2023\/9050763","article-title":"Electroacupuncture alleviates pain responses and inflammation in collagen-induced arthritis rats via suppressing the TLR2\/4-MyD88-NF-\u03baB signaling pathway","volume":"2023","author":"Sun","year":"2023","journal-title":"Evid Based Complement Alternat Med"},{"key":"2026052919400582300_vkag083-B28","first-page":"26","article-title":"Targeting NF-\u03baB and TNF-\u03b1 activation by electroacupuncture to suppress collagen-induced rheumatoid arthritis in model rats","volume":"21","author":"Li","year":"2015","journal-title":"Altern Ther Health Med"},{"key":"2026052919400582300_vkag083-B29","doi-asserted-by":"crossref","first-page":"1233","DOI":"10.1007\/s10753-020-01203-2","article-title":"Electroacupuncture relieves pain and attenuates inflammation progression through inducing IL-10 production in CFA-induced mice","volume":"43","author":"Yu","year":"2020","journal-title":"Inflammation"},{"key":"2026052919400582300_vkag083-B30","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.joim.2025.02.002","article-title":"Therapeutic components of acupuncture stimulation based on characteristics of sensory nerve and nervous signaling pathway","volume":"23","author":"Wie","year":"2025","journal-title":"J Integr Med"},{"key":"2026052919400582300_vkag083-B31","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1177\/09645284241298718","article-title":"High-intensity electroacupuncture is superior to low-intensity electroacupuncture for knee osteoarthritis: a meta-analysis of randomized controlled trials","volume":"42","author":"Yuan","year":"2024","journal-title":"Acupunct Med"},{"key":"2026052919400582300_vkag083-B32","doi-asserted-by":"crossref","first-page":"3243","DOI":"10.1016\/j.neuron.2025.06.023","article-title":"Neuroanatomical organization of electroacupuncture in modulating gastric function in mice and humans","volume":"113","author":"Dong","year":"2025","journal-title":"Neuron"},{"key":"2026052919400582300_vkag083-B33","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1016\/j.neuron.2020.07.015","article-title":"Somatotopic organization and intensity dependence in driving distinct NPY-expressing sympathetic pathways by electroacupuncture","volume":"108","author":"Liu","year":"2020","journal-title":"Neuron"},{"key":"2026052919400582300_vkag083-B34","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1038\/s41586-021-04001-4","article-title":"A neuroanatomical basis for electroacupuncture to drive the vagal-adrenal axis","volume":"598","author":"Liu","year":"2021","journal-title":"Nature"},{"key":"2026052919400582300_vkag083-B35","doi-asserted-by":"crossref","first-page":"107779","DOI":"10.4239\/wjd.v16.i8.107779","article-title":"Electroacupuncture with different current intensities can improve gastrointestinal motility in diabetic gastroparesis via vagal and sympathetic pathways","volume":"16","author":"Tang","year":"2025","journal-title":"World J Diabetes"},{"key":"2026052919400582300_vkag083-B36","doi-asserted-by":"crossref","first-page":"98","DOI":"10.20473\/fmi.v52i2.5219","article-title":"The potency of alpha-lipoic acid as anti-inflammatory on complete Freund\u2019s adjuvant-induced rheumatoid arthritis in rats","volume":"52","author":"Megawati","year":"2017","journal-title":"Folia Med Indones"},{"key":"2026052919400582300_vkag083-B37","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1007\/s00296-006-0193-5","article-title":"Alpha-lipoic acid suppresses the development of collagen-induced arthritis and protects against bone destruction in mice","volume":"27","author":"Lee","year":"2007","journal-title":"Rheumatol Int"},{"key":"2026052919400582300_vkag083-B38","doi-asserted-by":"crossref","first-page":"7522","DOI":"10.1074\/jbc.TM117.000259","article-title":"Lipoic acid metabolism and mitochondrial redox regulation","volume":"293","author":"Solmonson","year":"2018","journal-title":"J Biol Chem"},{"key":"2026052919400582300_vkag083-B39","first-page":"570","article-title":"Lipoic acid\u2014the drug of the future?","volume":"57","author":"Bilska","year":"2005","journal-title":"Pharmacol Rep"},{"key":"2026052919400582300_vkag083-B40","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1038\/s41589-019-0291-9","article-title":"Mitochondrial metabolism promotes adaptation to proteotoxic stress","volume":"15","author":"Tsvetkov","year":"2019","journal-title":"Nat Chem Biol"},{"key":"2026052919400582300_vkag083-B41","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1007\/s12011-022-03148-z","article-title":"Circulating level of blood iron and copper associated with inflammation and disease activity of rheumatoid arthritis","volume":"201","author":"Wang","year":"2023","journal-title":"Biol Trace Elem Res"},{"key":"2026052919400582300_vkag083-B42","doi-asserted-by":"crossref","first-page":"103484","DOI":"10.1016\/j.jaut.2025.103484","article-title":"The double-edged sword role of copper in rheumatoid arthritis: mechanisms, therapeutics, and challenges","volume":"157","author":"Guan","year":"2025","journal-title":"J Autoimmun"}],"container-title":["The Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/215\/5\/vkag083\/68434034\/vkag083.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/215\/5\/vkag083\/68434034\/vkag083.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T23:40:19Z","timestamp":1780098019000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jimmunol\/article\/doi\/10.1093\/jimmun\/vkag083\/8698278"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5]]},"references-count":42,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2026,5,14]]}},"URL":"https:\/\/doi.org\/10.1093\/jimmun\/vkag083","relation":{},"ISSN":["0022-1767","1550-6606"],"issn-type":[{"value":"0022-1767","type":"print"},{"value":"1550-6606","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,5]]},"published":{"date-parts":[[2026,5]]},"article-number":"vkag083"}}