{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T07:42:20Z","timestamp":1793259740999,"version":"4.5.0"},"reference-count":40,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T00:00:00Z","timestamp":1764115200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005088","name":"Beijing Municipal Health Commission","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005088","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004826","name":"Beijing Natural Science Foundation","doi-asserted-by":"publisher","award":["L222089"],"award-info":[{"award-number":["L222089"]}],"id":[{"id":"10.13039\/501100004826","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82202719"],"award-info":[{"award-number":["82202719"]}],"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":[[2025,12]]},"DOI":"10.1016\/j.phymed.2025.157562","type":"journal-article","created":{"date-parts":[[2025,11,20]],"date-time":"2025-11-20T14:57:19Z","timestamp":1763650639000},"page":"157562","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":3,"special_numbering":"C","title":["Targeting neuregulin-1 in cartilage homeostasis restoration: Kaempferol-3-o-rutinoside as a novel treatment for osteoarthritis"],"prefix":"10.1016","volume":"149","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-3168-5390","authenticated-orcid":false,"given":"Yueyang","family":"Sheng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0272-6193","authenticated-orcid":false,"given":"Shan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3568-2211","authenticated-orcid":false,"given":"Xinyu","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0319-9273","authenticated-orcid":false,"given":"Penglei","family":"Cui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongcan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2873-7197","authenticated-orcid":false,"given":"Ying","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7939-7666","authenticated-orcid":false,"given":"Yanzhuo","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3988-2779","authenticated-orcid":false,"given":"Qianqian","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2737-4048","authenticated-orcid":false,"given":"Chao","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-9226-5971","authenticated-orcid":false,"given":"Jianfeng","family":"Tao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6366-4758","authenticated-orcid":false,"given":"Chengai","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5546-0192","authenticated-orcid":false,"given":"Xu","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"11","key":"10.1016\/j.phymed.2025.157562_bib0001","doi-asserted-by":"crossref","first-page":"1097","DOI":"10.1016\/j.autrev.2018.06.002","article-title":"Osteoarthritis and its management - epidemiology, nutritional aspects and environmental factors","volume":"17","author":"Bortoluzzi","year":"2018","journal-title":"Autoimmun. Rev."},{"key":"10.1016\/j.phymed.2025.157562_bib0002","article-title":"IGF1 and NRG1 enhance proliferation, metabolic maturity, and the force-frequency response in hESC-derived engineered cardiac tissues","volume":"2017","author":"Cassady","year":"2017","journal-title":"Stem Cells Int."},{"issue":"Suppl 3","key":"10.1016\/j.phymed.2025.157562_bib0029","doi-asserted-by":"crossref","first-page":"S17","DOI":"10.1016\/j.joca.2010.05.025","article-title":"The OARSI histopathology initiative \u2013 recommendations for histological assessments of osteoarthritis in the mouse","volume":"18","author":"Glasson","year":"2010","journal-title":"Osteoarthritis and Cartilage"},{"key":"10.1016\/j.phymed.2025.157562_bib0003","doi-asserted-by":"crossref","DOI":"10.1016\/j.phymed.2020.153400","article-title":"The binding of kaempferol-3-O-rutinoside to vascular endothelial growth factor potentiates anti-inflammatory efficiencies in lipopolysaccharide-treated mouse macrophage RAW264.7 cells","volume":"80","author":"Hu","year":"2021","journal-title":"Phytomedicine"},{"issue":"10","key":"10.1016\/j.phymed.2025.157562_bib0004","doi-asserted-by":"crossref","DOI":"10.1111\/jfbc.14305","article-title":"Kaempferol-3-O-rutinoside exerts cardioprotective effects through NF-\u03baB\/NLRP3\/Caspase-1 pathway in ventricular remodeling after acute myocardial infarction","volume":"46","author":"Hua","year":"2022","journal-title":"J. Food Biochem."},{"issue":"7","key":"10.1016\/j.phymed.2025.157562_bib0005","doi-asserted-by":"crossref","DOI":"10.1111\/jfbc.13749","article-title":"Rat plasma protein binding of kaempferol-3-O-rutinoside from Lu'an GuaPian tea and its anti-inflammatory mechanism for cardiovascular protection","volume":"45","author":"Hua","year":"2021","journal-title":"J. Food Biochem."},{"key":"10.1016\/j.phymed.2025.157562_bib0006","article-title":"Low-intensity pulsed ultrasound promotes proliferation and myelinating genes expression of schwann cells through NRG1\/ErbB signaling pathway","volume":"80","author":"Huang","year":"2022","journal-title":"Tissue Cell"},{"issue":"6","key":"10.1016\/j.phymed.2025.157562_bib0007","first-page":"2321","article-title":"Kaempferol-3-O-\u03b2-rutinoside suppresses the inflammatory responses in lipopolysaccharide stimulated RAW264.7 cells via the NF \u03baB and MAPK pathways","volume":"44","author":"Hwang","year":"2019","journal-title":"Int. J. Mol. Med."},{"issue":"12","key":"10.1016\/j.phymed.2025.157562_bib0008","doi-asserted-by":"crossref","first-page":"2277","DOI":"10.3390\/molecules24122277","article-title":"Kaempferol: a key emphasis to its anticancer potential","volume":"24","author":"Imran","year":"2019","journal-title":"Molecules"},{"issue":"1","key":"10.1016\/j.phymed.2025.157562_bib0009","first-page":"73","article-title":"Living hybrid material based on probiotic with photothermal properties inhibits PD-L1 expression after tumouricidal photothermal therapy","volume":"6","author":"Jiang","year":"2025","journal-title":"Biomater. Transl."},{"issue":"1","key":"10.1016\/j.phymed.2025.157562_bib0010","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1038\/nrrheum.2010.196","article-title":"Role of proinflammatory cytokines in the pathophysiology of osteoarthritis","volume":"7","author":"Kapoor","year":"2011","journal-title":"Nat. Rev. Rheumatol."},{"issue":"16","key":"10.1016\/j.phymed.2025.157562_bib0011","doi-asserted-by":"crossref","first-page":"1648","DOI":"10.3390\/healthcare12161648","article-title":"Cartilage integrity: a review of mechanical and frictional properties and repair approaches in osteoarthritis","volume":"12","author":"Krakowski","year":"2024","journal-title":"Healthcare (Basel)"},{"issue":"1","key":"10.1016\/j.phymed.2025.157562_bib0012","doi-asserted-by":"crossref","first-page":"6336","DOI":"10.1038\/s41467-021-26422-5","article-title":"NRG1\/ErbB signalling controls the dialogue between macrophages and neural crest-derived cells during zebrafish fin regeneration","volume":"12","author":"Laplace-Builh\u00e9","year":"2021","journal-title":"Nat. Commun."},{"issue":"1","key":"10.1016\/j.phymed.2025.157562_bib0013","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1186\/s11658-022-00365-1","article-title":"Artemisinin relieves osteoarthritis by activating mitochondrial autophagy through reducing TNFSF11 expression and inhibiting PI3K\/AKT\/mTOR signaling in cartilage","volume":"27","author":"Li","year":"2022","journal-title":"Cell Mol. Biol. Lett."},{"issue":"7","key":"10.1016\/j.phymed.2025.157562_bib0014","doi-asserted-by":"crossref","first-page":"1172","DOI":"10.1002\/art.42089","article-title":"Prevalence trends of site-specific osteoarthritis from 1990 to 2019: findings from the Global Burden of Disease Study 2019","volume":"74","author":"Long","year":"2022","journal-title":"Arthritis Rheumatol."},{"issue":"10","key":"10.1016\/j.phymed.2025.157562_bib0015","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1038\/s41584-021-00673-4","article-title":"Early-stage symptomatic osteoarthritis of the knee - time for action","volume":"17","author":"Mahmoudian","year":"2021","journal-title":"Nat. Rev. Rheumatol."},{"key":"10.1016\/j.phymed.2025.157562_bib0016","doi-asserted-by":"crossref","unstructured":"Morris, G.M., Huey, R., Olson, A.J., 2008. Using AutoDock for ligand-receptor docking. Curr. Protoc. Bioinform. Chapter 8, Unit 8.14. doi:10.1002\/0471250953.bi0814s24.","DOI":"10.1002\/0471250953.bi0814s24"},{"issue":"10","key":"10.1016\/j.phymed.2025.157562_bib0017","doi-asserted-by":"crossref","first-page":"1225","DOI":"10.3390\/ph15101225","article-title":"Polyphenols, saponins and phytosterols in lentils and their health benefits: an overview","volume":"15","author":"Mustafa","year":"2022","journal-title":"Pharmaceuticals (Basel)"},{"issue":"1","key":"10.1016\/j.phymed.2025.157562_bib0018","doi-asserted-by":"crossref","first-page":"73","DOI":"10.4196\/kjpp.2024.28.1.73","article-title":"Naringenin modulates GABA mediated response in a sex-dependent manner in substantia gelatinosa neurons of trigeminal subnucleus caudalis in immature mice","volume":"28","author":"Park","year":"2024","journal-title":"Korean J. Physiol. Pharmacol."},{"key":"10.1016\/j.phymed.2025.157562_bib0020","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.arr.2017.07.004","article-title":"Aging and osteoarthritis: central role of the extracellular matrix","volume":"40","author":"Rahmati","year":"2017","journal-title":"Ageing Res. Rev."},{"issue":"2","key":"10.1016\/j.phymed.2025.157562_bib0021","doi-asserted-by":"crossref","first-page":"025210018","DOI":"10.36922\/OR025210018","article-title":"Materiobiology-driven engineering for next-generation organoids","volume":"1","author":"Reis","year":"2025","journal-title":"Organ. Res."},{"issue":"7","key":"10.1016\/j.phymed.2025.157562_bib0022","doi-asserted-by":"crossref","first-page":"e47","DOI":"10.1093\/nar\/gkv007","article-title":"limma powers differential expression analyses for RNA-sequencing and microarray studies","volume":"43","author":"Ritchie","year":"2015","journal-title":"Nucleic Acids Res."},{"issue":"1\u20132","key":"10.1016\/j.phymed.2025.157562_bib0023","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/j.cyto.2006.10.005","article-title":"IL-1beta, but not BMP-7 leads to a dramatic change in the gene expression pattern of human adult articular chondrocytes\u2013portraying the gene expression pattern in two donors","volume":"36","author":"Saas","year":"2006","journal-title":"Cytokine"},{"issue":"16","key":"10.1016\/j.phymed.2025.157562_bib0024","doi-asserted-by":"crossref","first-page":"3373","DOI":"10.1080\/10408398.2015.1126218","article-title":"Health benefits of walnut polyphenols: an exploration beyond their lipid profile","volume":"57","author":"S\u00e1nchez-Gonz\u00e1lez","year":"2017","journal-title":"Crit. Rev. Food Sci. Nutr."},{"issue":"1 Suppl","key":"10.1016\/j.phymed.2025.157562_bib0025","doi-asserted-by":"crossref","first-page":"215S","DOI":"10.1093\/ajcn\/81.1.215S","article-title":"Polyphenols: antioxidants and beyond","volume":"81","author":"Scalbert","year":"2005","journal-title":"Am. J. Clin. Nutr."},{"issue":"5\u20136","key":"10.1016\/j.phymed.2025.157562_bib0026","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1016\/j.aanat.2005.06.007","article-title":"Curcumin protects human chondrocytes from IL-l1beta-induced inhibition of collagen type II and beta1-integrin expression and activation of caspase-3: an immunomorphological study","volume":"187","author":"Shakibaei","year":"2005","journal-title":"Ann. Anat."},{"issue":"1","key":"10.1016\/j.phymed.2025.157562_bib0027","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1056\/NEJMcp1903768","article-title":"Osteoarthritis of the Knee","volume":"384","author":"Sharma","year":"2021","journal-title":"N. Engl. J. Med"},{"issue":"3","key":"10.1016\/j.phymed.2025.157562_bib0028","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1159\/000055915","article-title":"Interleukin-1beta induces different gene expression of stromelysin, aggrecan and tumor-necrosis-factor-stimulated gene 6 in human osteoarthritic chondrocytes in vitro","volume":"68","author":"St\u00f6ve","year":"2000","journal-title":"Pathobiology"},{"key":"10.1016\/j.phymed.2025.157562_bib0030","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.addr.2015.11.001","article-title":"Extracellular matrix structure","volume":"97","author":"Theocharis","year":"2016","journal-title":"Adv. Drug Deliv. Rev."},{"issue":"5","key":"10.1016\/j.phymed.2025.157562_bib0031","doi-asserted-by":"crossref","first-page":"H934","DOI":"10.1152\/ajpheart.00206.2017","article-title":"Inhibitory actions of the NRG-1\/ErbB4 pathway in macrophages during tissue fibrosis in the heart, skin, and lung","volume":"313","author":"Vermeulen","year":"2017","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"issue":"2","key":"10.1016\/j.phymed.2025.157562_bib0032","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1016\/j.jfda.2014.10.002","article-title":"Hepatoprotective effects of kaempferol 3-O-rutinoside and kaempferol 3-O-glucoside from Carthamus tinctorius L. on CCl4-induced oxidative liver injury in mice","volume":"23","author":"Wang","year":"2015","journal-title":"J. Food Drug Anal."},{"key":"10.1016\/j.phymed.2025.157562_bib0019","doi-asserted-by":"crossref","unstructured":"Wang, Y., Bryant, S.H., Cheng, T., Wang, J., Gindulyte, A., Shoemaker, B.A., Thiessen, P.A., He, S., Zhang, J., 2017. PubChem BioAssay: 2017 update. Nucleic Acids Res. 45(D1), D955\u2013D963.","DOI":"10.1093\/nar\/gkw1118"},{"issue":"1","key":"10.1016\/j.phymed.2025.157562_bib0033","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1302\/2046-3758.131.BJR-2023-0016.R2","article-title":"The CREB1 inhibitor 666-15 maintains cartilage homeostasis and mitigates osteoarthritis progression","volume":"13","author":"Wang","year":"2024","journal-title":"Bone Jt. Res."},{"issue":"3","key":"10.1016\/j.phymed.2025.157562_bib0034","article-title":"clusterProfiler 4.0: a universal enrichment tool for interpreting omics data","volume":"2","author":"Wu","year":"2021","journal-title":"Innovation (Camb)."},{"issue":"4","key":"10.1016\/j.phymed.2025.157562_bib0035","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1002\/jor.25420","article-title":"Eugenol protects chondrocytes and articular cartilage by downregulating the JAK3\/STAT4 signaling pathway","volume":"41","author":"Wu","year":"2023","journal-title":"J. Orthop. Res."},{"key":"10.1016\/j.phymed.2025.157562_bib0036","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1016\/j.ijbiomac.2021.02.029","article-title":"SIRT3 ameliorates osteoarthritis via regulating chondrocyte autophagy and apoptosis through the PI3K\/Akt\/mTOR pathway","volume":"175","author":"Xu","year":"2021","journal-title":"Int. J. Biol. Macromol."},{"issue":"1","key":"10.1016\/j.phymed.2025.157562_bib0037","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1038\/s41392-023-01330-w","article-title":"Osteoarthritis: pathogenic signaling pathways and therapeutic targets","volume":"8","author":"Yao","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"issue":"Pt B","key":"10.1016\/j.phymed.2025.157562_bib0038","article-title":"PP2 alleviates the progression of osteoarthritis by inhibiting Wnt\/\u03b2-catenin and activating TGF-\u03b2\/Smad signaling","volume":"124","author":"Zhang","year":"2023","journal-title":"Int. Immunopharmacol."},{"issue":"1","key":"10.1016\/j.phymed.2025.157562_bib0039","first-page":"89","article-title":"HIF-1\u03b1: linking subchondral bone and cartilage as a therapeutic target in osteoarthritis","volume":"5","author":"Zhang","year":"2024","journal-title":"Biomater. Transl."},{"key":"10.1016\/j.phymed.2025.157562_bib0040","first-page":"8641","article-title":"Cartilage-on-chip for osteoarthritis drug screening","volume":"1","author":"Zhao","year":"2025"}],"container-title":["Phytomedicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0944711325011985?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0944711325011985?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T15:47:43Z","timestamp":1773848863000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0944711325011985"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12]]},"references-count":40,"alternative-id":["S0944711325011985"],"URL":"https:\/\/doi.org\/10.1016\/j.phymed.2025.157562","relation":{},"ISSN":["0944-7113"],"issn-type":[{"value":"0944-7113","type":"print"}],"subject":[],"published":{"date-parts":[[2025,12]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Targeting neuregulin-1 in cartilage homeostasis restoration: Kaempferol-3-o-rutinoside as a novel treatment for osteoarthritis","name":"articletitle","label":"Article Title"},{"value":"Phytomedicine","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.phymed.2025.157562","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 GmbH.","name":"copyright","label":"Copyright"}],"article-number":"157562"}}