{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T16:21:15Z","timestamp":1791649275044,"version":"4.3.4"},"reference-count":36,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,5,27]],"date-time":"2025-05-27T00:00:00Z","timestamp":1748304000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Cellular Signalling"],"published-print":{"date-parts":[[2025,10]]},"DOI":"10.1016\/j.cellsig.2025.111905","type":"journal-article","created":{"date-parts":[[2025,5,27]],"date-time":"2025-05-27T02:41:54Z","timestamp":1748313714000},"page":"111905","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":6,"special_numbering":"C","title":["Effects of higenamine on M1\/M2 polarization and osteoclast differentiation in rheumatoid arthritis via the THBS-1\/TGF-\u03b2 signaling pathway"],"prefix":"10.1016","volume":"134","author":[{"given":"De-ta","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zi-jian","family":"Wan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-ping","family":"Sheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wu","family":"Rao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin-hua","family":"Zhan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing-liang","family":"Gu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xian-zhen","family":"Wei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tian-you","family":"Fan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"23","key":"10.1016\/j.cellsig.2025.111905_bb0005","doi-asserted-by":"crossref","first-page":"2205","DOI":"10.1056\/NEJMra1004965","article-title":"The pathogenesis of rheumatoid arthritis","volume":"365","author":"Mcinnes","year":"2011","journal-title":"N. Engl. J. Med."},{"issue":"3","key":"10.1016\/j.cellsig.2025.111905_bb0010","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1007\/s11427-020-1939-1","article-title":"Punicalagin ameliorates collagen-induced arthritis by downregulating m1 macrophage and pyroptosis via nf-kappab signaling pathway","volume":"65","author":"Ge","year":"2022","journal-title":"Sci. China-Life Sci."},{"issue":"1","key":"10.1016\/j.cellsig.2025.111905_bb0015","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1038\/s41590-020-00816-x","article-title":"The immunology of rheumatoid arthritis","volume":"22","author":"Weyand","year":"2021","journal-title":"Nat. Immunol."},{"key":"10.1016\/j.cellsig.2025.111905_bb0020","doi-asserted-by":"crossref","first-page":"1668","DOI":"10.3389\/fimmu.2020.01668","article-title":"Hypoxia-inducible factor is critical for pathogenesis and regulation of immune cell functions in rheumatoid arthritis","volume":"11","author":"Guo","year":"2020","journal-title":"Front. Immunol."},{"issue":"12","key":"10.1016\/j.cellsig.2025.111905_bb0025","first-page":"2675","article-title":"Progress of aconite compound in an animal model of rheumatoid arthritis","volume":"46","author":"Chen","year":"2019","journal-title":"Liaoning J TCM"},{"issue":"1","key":"10.1016\/j.cellsig.2025.111905_bb0030","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-021-02167-5","article-title":"Revealing the efficacy-toxicity relationship of fuzi in treating rheumatoid arthritis by systems pharmacology","volume":"11","author":"Feng","year":"2021","journal-title":"Sci. Rep."},{"key":"10.1016\/j.cellsig.2025.111905_bb0035","doi-asserted-by":"crossref","DOI":"10.1016\/j.jep.2022.115838","article-title":"Ethnopharmacological use, pharmacology, toxicology, phytochemistry, and progress in chinese crude drug processing of the lateral root of aconitum carmichaelii debeaux. (Fuzi): a review","volume":"301","author":"Wang","year":"2023","journal-title":"J. Ethnopharmacol."},{"key":"10.1016\/j.cellsig.2025.111905_bb0040","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.jchromb.2018.11.015","article-title":"Non-target metabonomic method provided new insights on the therapeutical mechanism of gancao fuzi decoction on rheumatoid arthritis rats","volume":"1105","author":"Liu","year":"2019","journal-title":"J. Chromatogr. B"},{"key":"10.1016\/j.cellsig.2025.111905_bb0045","doi-asserted-by":"crossref","DOI":"10.1016\/j.jep.2022.115837","article-title":"Gancao fuzi decoction regulates the th17\/treg cell imbalance in rheumatoid arthritis by targeting foxp3 via mir-34a","volume":"301","author":"Zhao","year":"2023","journal-title":"J. Ethnopharmacol."},{"key":"10.1016\/j.cellsig.2025.111905_bb0050","doi-asserted-by":"crossref","DOI":"10.1016\/j.jep.2024.118268","article-title":"Network pharmacology combined with affinity ultrafiltration to elucidate the potential compounds of shaoyao gancao fuzi decoction for the treatment of rheumatoid arthritis","volume":"330","author":"Fu","year":"2024","journal-title":"J. Ethnopharmacol."},{"key":"10.1016\/j.cellsig.2025.111905_bb0055","doi-asserted-by":"crossref","DOI":"10.1016\/j.jep.2024.117910","article-title":"Integration of serum pharmacochemistry and metabolomics to reveal the underlying mechanism of shaoyao-gancao-fuzi decoction to ameliorate rheumatoid arthritis","volume":"326","author":"Li","year":"2024","journal-title":"J. Ethnopharmacol."},{"key":"10.1016\/j.cellsig.2025.111905_bb0060","doi-asserted-by":"crossref","first-page":"1035","DOI":"10.3389\/fphar.2020.01035","article-title":"Uncovering the complexity mechanism of different formulas treatment for rheumatoid arthritis based on a novel network pharmacology model","volume":"11","author":"Wang","year":"2020","journal-title":"Front. Pharmacol."},{"issue":"1","key":"10.1016\/j.cellsig.2025.111905_bb0065","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1248\/cpb.24.176","article-title":"Letter: studies on cardiac principle of aconite root","volume":"24","author":"Kosuge","year":"1976","journal-title":"Chem. Pharm. Bull."},{"issue":"4","key":"10.1016\/j.cellsig.2025.111905_bb0070","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1139\/y94-049","article-title":"Different pharmacological characteristics of structurally similar benzylisoquinoline analogs, papaverine, higenamine, and gs 389, on isolated rat aorta and heart","volume":"72","author":"Chang","year":"1994","journal-title":"Can. J. Physiol. Pharmacol."},{"key":"10.1016\/j.cellsig.2025.111905_bb0075","doi-asserted-by":"crossref","DOI":"10.1016\/j.intimp.2020.106629","article-title":"Anti-inflammatory effects of higenamine (hig) on lps-activated mouse microglia (bv2) through nf-kappab and nrf2\/ho-1 signaling pathways","volume":"85","author":"Yang","year":"2020","journal-title":"Int. Immunopharmacol."},{"issue":"4","key":"10.1016\/j.cellsig.2025.111905_bb0080","doi-asserted-by":"crossref","DOI":"10.1177\/1559325820972205","article-title":"Neuroprotective effects of higenamine against the alzheimer\u2019s disease via amelioration of cognitive impairment, abeta burden, apoptosis and regulation of akt\/gsk3beta signaling pathway","volume":"18","author":"Yang","year":"2020","journal-title":"Dose-Response"},{"issue":"1","key":"10.1016\/j.cellsig.2025.111905_bb0085","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1186\/s13020-020-00403-0","article-title":"Metabolomics coupled with integrated approaches reveal the therapeutic effects of higenamine combined with [6]-gingerol on doxorubicin-induced chronic heart failure in rats","volume":"15","author":"Wen","year":"2020","journal-title":"Chin. Med."},{"issue":"5","key":"10.1016\/j.cellsig.2025.111905_bb0090","doi-asserted-by":"crossref","first-page":"3107","DOI":"10.3892\/etm.2016.3730","article-title":"Protective effect of higenamine ameliorates collagen-induced arthritis through heme oxygenase-1 and pi3k\/akt\/nrf-2 signaling pathways","volume":"12","author":"Duan","year":"2016","journal-title":"Exp. Ther. Med."},{"key":"10.1016\/j.cellsig.2025.111905_bb0095","doi-asserted-by":"crossref","DOI":"10.1016\/j.phymed.2021.153801","article-title":"Anti-inflammatory and osteoprotective effects of chikusetsusaponin iva on rheumatoid arthritis via the jak\/stat signaling pathway","volume":"93","author":"Guo","year":"2021","journal-title":"Phytomedicine"},{"key":"10.1016\/j.cellsig.2025.111905_bb0100","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1186\/s12950-015-0072-5","article-title":"Expression of hedgehog signal pathway in articular cartilage is associated with the severity of cartilage damage in rats with adjuvant-induced arthritis","volume":"12","author":"Li","year":"2015","journal-title":"J. Inflamm.-Lond."},{"issue":"Suppl. 3","key":"10.1016\/j.cellsig.2025.111905_bb0105","doi-asserted-by":"crossref","first-page":"S17","DOI":"10.1016\/j.joca.2010.05.025","article-title":"The oarsi histopathology initiative - recommendations for histological assessments of osteoarthritis in the mouse","volume":"18","author":"Glasson","year":"2010","journal-title":"Osteoarthr. Cartil."},{"key":"10.1016\/j.cellsig.2025.111905_bb0110","article-title":"Pharmacological effects of higenamine based on signalling pathways and mechanism of action","volume":"13","author":"Chen","year":"2022","journal-title":"Front. Pharmacol."},{"issue":"1","key":"10.1016\/j.cellsig.2025.111905_bb0115","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1002\/jbmr.2308","article-title":"Thrombospondin-1 regulates bone homeostasis through effects on bone matrix integrity and nitric oxide signaling in osteoclasts","volume":"30","author":"Amend","year":"2015","journal-title":"J. Bone Miner. Res."},{"issue":"3","key":"10.1016\/j.cellsig.2025.111905_bb0120","doi-asserted-by":"crossref","first-page":"338","DOI":"10.2174\/157016110791112296","article-title":"The axis of thrombospondin-1, transforming growth factor beta and connective tissue growth factor: an emerging therapeutic target in rheumatoid arthritis","volume":"8","author":"Rico","year":"2010","journal-title":"Curr. Vasc. Pharmacol."},{"issue":"3","key":"10.1016\/j.cellsig.2025.111905_bb0125","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1016\/j.bbrc.2012.05.020","article-title":"Thrombospondin-1 inhibits osteogenic differentiation of human mesenchymal stem cells through latent tgf-beta activation","volume":"422","author":"Bailey","year":"2012","journal-title":"Biochem. Biophys. Res. Commun."},{"issue":"3","key":"10.1016\/j.cellsig.2025.111905_bb0130","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1016\/j.ajpath.2015.11.003","article-title":"Inhibition of transforming growth factor-\u03b2 activation diminishes tumor progression and osteolytic bone disease in mouse models of multiple myeloma","volume":"186","author":"Lu","year":"2016","journal-title":"Am. J. Pathol."},{"key":"10.1016\/j.cellsig.2025.111905_bb0135","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2022.1034050","article-title":"Regulation of differentiation and generation of osteoclasts in rheumatoid arthritis","volume":"13","author":"Niu","year":"2022","journal-title":"Front. Immunol."},{"issue":"3","key":"10.1016\/j.cellsig.2025.111905_bb0140","doi-asserted-by":"crossref","DOI":"10.1016\/j.autrev.2021.102758","article-title":"Novel insights into macrophage diversity in rheumatoid arthritis synovium","volume":"20","author":"Boutet","year":"2021","journal-title":"Autoimmun. Rev."},{"key":"10.1016\/j.cellsig.2025.111905_bb0145","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/j.bcp.2019.03.029","article-title":"The many facets of macrophages in rheumatoid arthritis","volume":"165","author":"Siouti","year":"2019","journal-title":"Biochem. Pharmacol."},{"issue":"12","key":"10.1016\/j.cellsig.2025.111905_bb0150","doi-asserted-by":"crossref","first-page":"1953","DOI":"10.1002\/jssc.201300012","article-title":"Simultaneous quantitation of seven alkaloids in processed fuzi decoction by rapid resolution liquid chromatography coupled with tandem mass spectrometry","volume":"36","author":"Guo","year":"2013","journal-title":"J. Sep. Sci."},{"issue":"10","key":"10.1016\/j.cellsig.2025.111905_bb0155","doi-asserted-by":"crossref","first-page":"1776","DOI":"10.1002\/dta.3132","article-title":"Blood-to-muscle distribution and urinary excretion of higenamine in rats","volume":"13","author":"Chang","year":"2021","journal-title":"Drug Test Anal."},{"issue":"1","key":"10.1016\/j.cellsig.2025.111905_bb0160","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1007\/BF02976436","article-title":"Inhibition of lipopolysaccharide-induced inducible nitric oxide (inos) mrna expression and nitric oxide production by higenamine in murine peritoneal macrophages","volume":"22","author":"Lee","year":"1999","journal-title":"Arch. Pharm. Res."},{"issue":"1","key":"10.1016\/j.cellsig.2025.111905_bb0165","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1016\/S0022-3565(24)35103-1","article-title":"Inhibition of activation of nuclear factor kappab is responsible for inhibition of inducible nitric oxide synthase expression by higenamine, an active component of aconite root","volume":"291","author":"Kang","year":"1999","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"10.1016\/j.cellsig.2025.111905_bb0170","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2022.867368","article-title":"Pathological osteoclasts and precursor macrophages in inflammatory arthritis","volume":"13","author":"Hasegawa","year":"2022","journal-title":"Front. Immunol."},{"key":"10.1016\/j.cellsig.2025.111905_bb0175","doi-asserted-by":"crossref","first-page":"1062","DOI":"10.3389\/fimmu.2017.01062","article-title":"Microrna: dynamic regulators of macrophage polarization and plasticity","volume":"8","author":"Self-Fordham","year":"2017","journal-title":"Front. Immunol."},{"issue":"5","key":"10.1016\/j.cellsig.2025.111905_bb0180","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1002\/jbmr.4800","article-title":"Higenamine promotes osteogenesis via iqgap1\/smad4 signaling pathway and prevents age- and estrogen-dependent bone loss in mice","volume":"38","author":"Dong","year":"2023","journal-title":"J. Bone Miner. Res."}],"container-title":["Cellular Signalling"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0898656825003201?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0898656825003201?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,11,5]],"date-time":"2025-11-05T04:30:44Z","timestamp":1762317044000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0898656825003201"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10]]},"references-count":36,"alternative-id":["S0898656825003201"],"URL":"https:\/\/doi.org\/10.1016\/j.cellsig.2025.111905","relation":{},"ISSN":["0898-6568"],"issn-type":[{"value":"0898-6568","type":"print"}],"subject":[],"published":{"date-parts":[[2025,10]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Effects of higenamine on M1\/M2 polarization and osteoclast differentiation in rheumatoid arthritis via the THBS-1\/TGF-\u03b2 signaling pathway","name":"articletitle","label":"Article Title"},{"value":"Cellular Signalling","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.cellsig.2025.111905","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 The Authors. Published by Elsevier Inc.","name":"copyright","label":"Copyright"}],"article-number":"111905"}}