{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T21:03:21Z","timestamp":1768511001311,"version":"3.49.0"},"reference-count":47,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T00:00:00Z","timestamp":1767916800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2023YFF1105305"],"award-info":[{"award-number":["2023YFF1105305"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background: Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by synovitis. The prevalence of RA is estimated to be 0.5\u20131% worldwide. Methods: This work investigated the therapeutic effects and underlying mechanisms of blue mussel (Mytilus galloprovincialis) oil (BMO) on RA in rats, using green-lipped mussel oil (GMO) and Antarctic krill oil (KO) as controls. Results: The results suggested that BMO, GMO, and KO all alleviated paw swelling in rats and reduced serum levels of rheumatoid factor (RF), anti-cyclic citrullinated peptide (anti-CCP) antibody, and pro-inflammatory cytokines such as TNF-\u03b1 and IL-17. Histopathological assessment further revealed that BMO, GMO, and KO prevented synovial fibroplasia, mitigated inflammatory cell infiltration, and improved cartilage damage in ankle joints. Overall, BMO exhibited slightly superior alleviating effects compared with GMO and KO. Plasma lipidomics analysis revealed that the lipid metabolites altered by BMO showed significant correlations with RA-related indicators, particularly pro-inflammatory cytokines. Functional enrichment analysis suggested the involvement of inflammation-related pathways, particularly the NF-\u03baB signaling pathway. Further validation demonstrated that BMO effectively suppressed the production of inflammatory cytokines (TNF-\u03b1, IL-17) and the expression of NF-\u03baB p65, JAK2, and STAT3 proteins in synovial tissue. And IL-17 production in footpad tissues is closely associated with CD3-positive T cells. Similar effects were also observed for GMO and KO. Conclusions: Collectively, BMO might ameliorate RA by inhibiting NF-\u03baB and JAK2\/STAT3 signaling pathways.<\/jats:p>","DOI":"10.3390\/nu18020215","type":"journal-article","created":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T16:03:16Z","timestamp":1767974596000},"page":"215","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Therapeutic Effect and Underlying Mechanism of Blue Mussel (Mytilus galloprovincialis) Oil on Adjuvant-Induced Rheumatoid Arthritis in Rats"],"prefix":"10.3390","volume":"18","author":[{"given":"Xin","family":"Yu","sequence":"first","affiliation":[{"name":"College of Food Science and Engineering, Ocean University of China, Qingdao 266100, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xueyuan","family":"Fu","sequence":"additional","affiliation":[{"name":"Marine Biomedical Research Institute of Qingdao, Ocean University of China, Qingdao 266100, China"},{"name":"Qingdao Marine Biomedical Research Institute Co., Ltd., Qingdao 266100, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fen","family":"Du","sequence":"additional","affiliation":[{"name":"Marine Biomedical Research Institute of Qingdao, Ocean University of China, Qingdao 266100, China"},{"name":"Qingdao Marine Biomedical Research Institute Co., Ltd., Qingdao 266100, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chuyi","family":"Liu","sequence":"additional","affiliation":[{"name":"Marine Biomedical Research Institute of Qingdao, Ocean University of China, Qingdao 266100, China"},{"name":"Qingdao Marine Biomedical Research Institute Co., Ltd., Qingdao 266100, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Changwei","family":"Wang","sequence":"additional","affiliation":[{"name":"Marine Biomedical Research Institute of Qingdao, Ocean University of China, Qingdao 266100, China"},{"name":"Qingdao Marine Biomedical Research Institute Co., Ltd., Qingdao 266100, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaomei","family":"Feng","sequence":"additional","affiliation":[{"name":"Marine Biomedical Research Institute of Qingdao, Ocean University of China, Qingdao 266100, China"},{"name":"Qingdao Marine Biomedical Research Institute Co., Ltd., Qingdao 266100, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9112-0945","authenticated-orcid":false,"given":"Wanxiu","family":"Cao","sequence":"additional","affiliation":[{"name":"Marine Biomedical Research Institute of Qingdao, Ocean University of China, Qingdao 266100, China"},{"name":"Qingdao Marine Biomedical Research Institute Co., Ltd., Qingdao 266100, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7073-9626","authenticated-orcid":false,"given":"Qingjuan","family":"Tang","sequence":"additional","affiliation":[{"name":"College of Food Science and Engineering, Ocean University of China, Qingdao 266100, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1186\/s13075-017-1245-9","article-title":"Structural cartilage damage attracts circulating rheumatoid arthritis synovial fibroblasts into affected joints","volume":"19","author":"Hillen","year":"2017","journal-title":"Arthritis Res. Ther."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/j.cyto.2008.12.017","article-title":"Total alkaloids from Radix Linderae prevent the production of inflammatory mediators in lipopolysaccharide-stimulated RAW 264.7 cells by suppressing NF-\u03baB and MAPKs activation","volume":"46","author":"Luo","year":"2009","journal-title":"Cytokine"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1016\/j.autrev.2004.09.002","article-title":"Epidemiology of adult rheumatoid arthritis","volume":"4","author":"Alamanos","year":"2005","journal-title":"Autoimmun. Rev."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"119083","DOI":"10.1016\/j.lfs.2021.119083","article-title":"The role of myeloid-derived suppressor cells in rheumatoid arthritis: An update","volume":"269","author":"Navashenaq","year":"2021","journal-title":"Life Sci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"930","DOI":"10.1111\/cbdd.14015","article-title":"Some important inhibitors and mechanisms of rheumatoid arthritis","volume":"99","author":"Zhou","year":"2022","journal-title":"Chem. Biol. Drug Des."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1038\/s41584-022-00793-5","article-title":"Mechanisms of joint destruction in rheumatoid arthritis\u2014Immune cell\u2013fibroblast\u2013bone interactions","volume":"18","author":"Komatsu","year":"2022","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1679","DOI":"10.1056\/NEJMcibr2024718","article-title":"Fibroblasts in rheumatoid arthritis","volume":"383","author":"Chu","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.ejr.2014.06.004","article-title":"FoxP3+ T regulatory cells in Rheumatoid arthritis and the imbalance of the Treg\/TH17 cytokine axis","volume":"37","author":"Mamdouh","year":"2015","journal-title":"Egypt. Rheumatol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1007\/s10067-012-2041-1","article-title":"Advances in research on animal models of rheumatoid arthritis","volume":"32","author":"Hu","year":"2013","journal-title":"Clin. Rheumatol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/j.intimp.2015.12.029","article-title":"Anti-inflammatory effect of corymbocoumarin from Seseli gummiferum subsp. corymbosum through suppression of NF-\u03baB signaling pathway and induction of HO-1 expression in LPS-stimulated RAW 264.7 cells","volume":"31","author":"Chun","year":"2016","journal-title":"Int. Immunopharmacol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1016\/j.intimp.2015.01.001","article-title":"Expression and effects of B-lymphocyte stimulator and its receptors in T cell-mediated autoimmune arthritis","volume":"24","author":"Chang","year":"2015","journal-title":"Int. Immunopharmacol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"5303","DOI":"10.2147\/IJN.S213831","article-title":"Nanoformulations of natural products for management of metabolic syndrome","volume":"14","author":"Taghipour","year":"2019","journal-title":"Int. J. Nanomed."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"118786","DOI":"10.1016\/j.jep.2024.118786","article-title":"Xuetongsu ameliorates synovial inflammatory hyperplasia in rheumatoid arthritis by inhibiting JAK2\/STAT3 and NF-\u03baB signaling pathways","volume":"337","author":"Deng","year":"2025","journal-title":"J. Ethnopharmacol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1016\/j.foodchem.2016.06.094","article-title":"Identification of glycerophospholipid molecular species of mussel (Mytilus edulis) lipids by high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry","volume":"213","author":"Yin","year":"2016","journal-title":"Food Chem."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.plipres.2014.09.001","article-title":"Omega-3 long chain fatty acid \u201cbioavailability\u201d: A review of evidence and methodological considerations","volume":"56","author":"Ghasemifard","year":"2014","journal-title":"Prog. Lipid Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"106307","DOI":"10.1016\/j.jff.2024.106307","article-title":"Blue mussel (Mytilus edulis) lipid extract ameliorates insulin resistance in diabetic rats by regulating the SphK\/So1P signaling pathway","volume":"119","author":"Kuang","year":"2024","journal-title":"J. Funct. Foods"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Li, K., Song, X., Li, H., Kuang, X., Liu, S., Liu, R., and Li, D. (2024). Mussel oil is superior to fish oil in preventing atherosclerosis of ApoE-\/- mice. Front. Nutr., 11.","DOI":"10.3389\/fnut.2024.1326421"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1007\/s11745-007-3078-9","article-title":"Seasonal variations of lipid content and composition in Perna viridis","volume":"42","author":"Li","year":"2007","journal-title":"Lipids"},{"key":"ref_19","first-page":"274","article-title":"Biochemical composition, lipid classes, fatty acids and sexual hormones in the mussel Mytilus galloprovincialis from cultivated populations in south Spain","volume":"358","author":"Herrera","year":"2012","journal-title":"Aquaculture"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1038\/s41538-025-00546-0","article-title":"Effects of Mytilus edulis derived plasmalogens against atherosclerosis via lipid metabolism and MAPK signaling pathway","volume":"9","author":"Feng","year":"2025","journal-title":"NPJ Sci. Food"},{"key":"ref_21","first-page":"135146","article-title":"Acute Hepatitis Induced by Lyprinol, the Lipid Extract of the Green-Lipped Mussel (Perna canaliculus), in a Patient with Polyarthrosis","volume":"2012","author":"Abdulazim","year":"2012","journal-title":"Case Rep. Hepatol."},{"key":"ref_22","first-page":"212","article-title":"Clinical efficacy and safety of Lyprinol, a patented extract from New Zealand green-lipped mussel (Perna Canaliculus) in patients with osteoarthritis of the hip and knee: A multicenter 2-month clinical trial","volume":"35","author":"Cho","year":"2003","journal-title":"Eur. Ann. Allergy Clin. Immunol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"568","DOI":"10.3390\/md12020568","article-title":"Anti-inflammatory activity and mechanism of a lipid extract from hard-shelled mussel (Mytilus coruscus) on chronic arthritis in rats","volume":"12","author":"Li","year":"2014","journal-title":"Mar. Drugs"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"625","DOI":"10.3390\/nu7010625","article-title":"Lipid extract from hard-shelled mussel (Mytilus coruscus) improves clinical conditions of patients with rheumatoid arthritis: A randomized controlled trial","volume":"7","author":"Fu","year":"2015","journal-title":"Nutrients"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Lindqvist, H.M., Gjertsson, I., Eneljung, T., and Winkvist, A. (2018). Influence of blue mussel (Mytilus edulis) intake on disease activity in female patients with rheumatoid arthritis: The MIRA randomized cross-over dietary intervention. Nutrients, 10.","DOI":"10.3390\/nu10040481"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1136\/annrheumdis-2019-eular.3009","article-title":"Thu0180 influence of blue mussel (Mytilus edulis) intake on fatty acid composition in erythrocytes and plasma phospholipids and serum metabolites in women with rheumatoid arthritis","volume":"78","author":"Lindqvist","year":"2019","journal-title":"Ann. Rheum. Dis."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.plefa.2009.12.003","article-title":"Prophylactic and therapeutic effects of Mytilus edulis fatty acids on adjuvant-induced arthritis in male Wistar rats","volume":"82","author":"McPhee","year":"2010","journal-title":"Prostaglandins Leukot. Essent. Fat. Acids"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"106704","DOI":"10.1016\/j.ultsonch.2023.106704","article-title":"Application of an aqueous enzymatic\u2013ultrasound cavitation method for the separation of Sapium sebiferum seed kernel oil","volume":"101","author":"Liu","year":"2023","journal-title":"Ultrason. Sonochem."},{"key":"ref_29","first-page":"100","article-title":"Treatment of collagen-induced arthritis rat model by using Notch signalling inhibitor","volume":"28","author":"Chen","year":"2021","journal-title":"J. Orthop. Transl."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"149786","DOI":"10.1016\/j.ijbiomac.2025.149786","article-title":"Effect of berberine-loaded mesoporous silica nanoparticles and their combination with collagen\/hydroxyapatite sponge scaffold on the regeneration of rabbit skull defects","volume":"338","author":"Teimouri","year":"2025","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"9378","DOI":"10.1111\/jcmm.16877","article-title":"Ezrin regulates synovial angiogenesis in rheumatoid arthritis through YAP and Akt signalling","volume":"25","author":"Chen","year":"2021","journal-title":"J. Cell. Mol. Med."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Miller, M.R., Abshirini, M., Wolber, F.M., Tuterangiwhiu, T.R., and Kruger, M.C. (2023). Greenshell mussel products: A comprehensive review of sustainability, traditional use, and efficacy. Sustainability, 15.","DOI":"10.3390\/su15053912"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"672","DOI":"10.1093\/ajcn\/nqac125","article-title":"Krill oil improved osteoarthritic knee pain in adults with mild to moderate knee osteoarthritis: A 6-month multicenter, randomized, double-blind, placebo-controlled trial","volume":"116","author":"Stonehouse","year":"2022","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"5434","DOI":"10.53730\/ijhs.v6nS5.9829","article-title":"Assessment of auto-antibodies (RF, Anti-CCP, and anti-RA33) in rheumatoid arthritis patients: Comparative study","volume":"6","author":"Hashiam","year":"2022","journal-title":"Int. J. Health Sci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"133","DOI":"10.2147\/IJN.S289828","article-title":"Topical nano-vesicular spanlastics of celecoxib: Enhanced anti-inflammatory effect and down-regulation of TNF-\u03b1, NF-\u03baB and COX-2 in complete Freund\u2019s adjuvant-induced arthritis model in rats","volume":"16","author":"Alaaeldin","year":"2021","journal-title":"Int. J. Nanomed."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/j.ddmec.2006.06.004","article-title":"IL-1 in chronic arthritis, lessons from animal models","volume":"3","author":"Joosten","year":"2006","journal-title":"Drug Discov. Today Dis. Mech."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"210","DOI":"10.3904\/kjim.2016.329","article-title":"N-acetyl-l-cysteine controls osteoclastogenesis through regulating Th17 differentiation and RANKL in rheumatoid arthritis","volume":"34","author":"Kim","year":"2017","journal-title":"Korean J. Intern. Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"111933","DOI":"10.1016\/j.intimp.2024.111933","article-title":"TRPM7 facilitates fibroblast-like synoviocyte proliferation, metastasis and inflammation through increasing IL-6 stability via the PKC\u03b1-HuR axis in rheumatoid arthritis","volume":"132","author":"Lin","year":"2024","journal-title":"Int. Immunopharmacol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"v3","DOI":"10.1093\/rheumatology\/kes113","article-title":"Understanding the dynamics: Pathways involved in the pathogenesis of rheumatoid arthritis","volume":"51","author":"Choy","year":"2012","journal-title":"Rheumatology"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Siriarchavatana, P., Kruger, M.C., Miller, M.R., Tian, H., and Wolber, F.M. (2020). Effects of greenshell mussel (Perna canaliculus) intake on pathological markers of multiple phenotypes of osteoarthritis in rats. Appl. Sci., 10.","DOI":"10.3390\/app10176131"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Kumar, N.G., Contaifer, D., Madurantakam, P., Carbone, S., Price, E.T., Van Tassell, B., Brophy, D.F., and Wijesinghe, D.S. (2019). Dietary bioactive fatty acids as modulators of immune function: Implications on human health. Nutrients, 11.","DOI":"10.3390\/nu11122974"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1038\/s12276-022-00725-z","article-title":"Lipidome profile predictive of disease evolution and activity in rheumatoid arthritis","volume":"54","author":"Koh","year":"2022","journal-title":"Exp. Mol. Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.abb.2018.07.021","article-title":"Plasma lipidomic profile signature of rheumatoid arthritis versus Lyme arthritis patients","volume":"654","author":"Domingues","year":"2018","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1444","DOI":"10.1007\/s10753-024-01986-8","article-title":"Relationship between the lipidome profile and disease activity in patients with rheumatoid arthritis","volume":"47","author":"Masuoka","year":"2024","journal-title":"Inflammation"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"e20191123","DOI":"10.1084\/jem.20191123","article-title":"Targeting interleukin-17 in chronic inflammatory disease: A clinical perspective","volume":"217","author":"Zwicky","year":"2019","journal-title":"J. Exp. Med."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2786","DOI":"10.1111\/febs.14147","article-title":"Berberine ameliorates collagen-induced arthritis in rats by suppressing Th17 cell responses via inducing cortistatin in the gut","volume":"284","author":"Yue","year":"2017","journal-title":"FEBS J."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1627","DOI":"10.1111\/1756-185X.13958","article-title":"Nuclear factor-\u03baB in rheumatoid arthritis","volume":"23","author":"Li","year":"2020","journal-title":"Int. J. Rheum. Dis."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/18\/2\/215\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T06:10:42Z","timestamp":1768457442000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/18\/2\/215"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,9]]},"references-count":47,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2026,1]]}},"alternative-id":["nu18020215"],"URL":"https:\/\/doi.org\/10.3390\/nu18020215","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,9]]}}}