{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T01:32:59Z","timestamp":1792805579746,"version":"4.5.0"},"reference-count":34,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2024,11,30]],"date-time":"2024-11-30T00:00:00Z","timestamp":1732924800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Korea Medical Device Development Fund grant funded by the Korean government","award":["1415181807"],"award-info":[{"award-number":["1415181807"]}],"id":[{"id":"https:\/\/ror.org\/03g98ap29","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Korea Medical Device Development Fund grant funded by the Korean government","award":["RS-2021-KD000001"],"award-info":[{"award-number":["RS-2021-KD000001"]}],"id":[{"id":"https:\/\/ror.org\/03g98ap29","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Inflammatory disorders encompass a range of conditions, including osteoarthritis (OA), characterized by the body\u2019s heightened immune response to diverse stimuli. OA is a prevalent degenerative joint disease characterized by the progressive deterioration of joint cartilage and subchondral bone, leading to pain, limited mobility, and physical disability. Synovitis, the inflammation of the synovial membrane, is increasingly recognized as a critical factor in OA pathogenesis and progression. This study evaluates the therapeutic potential of cinnamaldehyde (CA), a bioactive compound derived from cinnamon, on synovial and articular inflammation in OA. Given CA\u2019s established anti-inflammatory, antioxidant, and antibacterial properties, this research explores its specific impact on OA and synovitis. The cytotoxicity of CA was assessed using a CCK-8 assay in human IL-1\u03b2 pretreated chondrocytes and synoviocytes, which serve as in vitro models of OA and synovitis. The study further examined the effects of CA on the expression of proinflammatory cytokines, including IL-6, COX-2, and TNF-\u03b1, utilizing multiple analytical techniques. Additionally, the production of matrix metalloproteinases (MMP-3 and MMP-13) and the activation of the NF-\u03baB signaling pathway, particularly the phosphorylation of p65 (pp65), were investigated. The role of the NF-\u03baB inhibitor 5HPP-33 and its downstream effects on gene expression, including COX-2 and IL-6, as well as the MAPK pathway components (p38, ERK, and JNK), were also explored. An MEK inhibitor (U0126) was employed to assess its downstream impact on COX-2 and IL-6 expressions. The results demonstrated that CA significantly inhibited the expression of proinflammatory cytokines and suppressed NF-\u03baB activation in IL-1\u03b2 pretreated chondrocytes and synoviocytes. These findings suggest that CA, in a dose-dependent manner, may serve as an effective therapeutic agent for preventing OA and synovitis, offering valuable insights into its potential role in managing synovial inflammation and OA.<\/jats:p>","DOI":"10.3390\/ijms252312914","type":"journal-article","created":{"date-parts":[[2024,12,2]],"date-time":"2024-12-02T05:43:43Z","timestamp":1733118223000},"page":"12914","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Cinnamaldehyde-Mediated Suppression of MMP-13, COX-2, and IL-6 Through MAPK and NF-\u03baB Signaling Inhibition in Chondrocytes and Synoviocytes Under Inflammatory Conditions"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5115-6062","authenticated-orcid":false,"given":"Jaishree","family":"Sankaranarayanan","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences, Chonnam National University Medical School, Hwasun 58128, Jeollanam-do, Republic of Korea"},{"name":"Department of Orthopaedic Surgery, Center for Joint Disease of Chonnam National University Hwasun Hospital, 322 Seoyang-ro, Hwasun 519-763, Jeollanam-do, Republic of Korea"},{"name":"Korea Biomedical Materials and Devices Innovation Research Center, Chonnam National University Hospital, 42 Jebong-ro, Dong-gu, Gwangju 501-757, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seok Cheol","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Center for Joint Disease of Chonnam National University Hwasun Hospital, 322 Seoyang-ro, Hwasun 519-763, Jeollanam-do, Republic of Korea"},{"name":"Korea Biomedical Materials and Devices Innovation Research Center, Chonnam National University Hospital, 42 Jebong-ro, Dong-gu, Gwangju 501-757, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyung Keun","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Center for Joint Disease of Chonnam National University Hwasun Hospital, 322 Seoyang-ro, Hwasun 519-763, Jeollanam-do, Republic of Korea"},{"name":"Korea Biomedical Materials and Devices Innovation Research Center, Chonnam National University Hospital, 42 Jebong-ro, Dong-gu, Gwangju 501-757, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ju Yeon","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Center for Joint Disease of Chonnam National University Hwasun Hospital, 322 Seoyang-ro, Hwasun 519-763, Jeollanam-do, Republic of Korea"},{"name":"Korea Biomedical Materials and Devices Innovation Research Center, Chonnam National University Hospital, 42 Jebong-ro, Dong-gu, Gwangju 501-757, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0708-6324","authenticated-orcid":false,"given":"Sree Samanvitha","family":"Kuppa","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Chonnam National University Medical School, Hwasun 58128, Jeollanam-do, Republic of Korea"},{"name":"Department of Orthopaedic Surgery, Center for Joint Disease of Chonnam National University Hwasun Hospital, 322 Seoyang-ro, Hwasun 519-763, Jeollanam-do, Republic of Korea"},{"name":"Korea Biomedical Materials and Devices Innovation Research Center, Chonnam National University Hospital, 42 Jebong-ro, Dong-gu, Gwangju 501-757, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jong Keun","family":"Seon","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Chonnam National University Medical School, Hwasun 58128, Jeollanam-do, Republic of Korea"},{"name":"Department of Orthopaedic Surgery, Center for Joint Disease of Chonnam National University Hwasun Hospital, 322 Seoyang-ro, Hwasun 519-763, Jeollanam-do, Republic of Korea"},{"name":"Korea Biomedical Materials and Devices Innovation Research Center, Chonnam National University Hospital, 42 Jebong-ro, Dong-gu, Gwangju 501-757, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1745","DOI":"10.1016\/S0140-6736(19)30417-9","article-title":"Osteoarthritis","volume":"393","author":"Hunter","year":"2019","journal-title":"Lancet"},{"key":"ref_2","unstructured":"GBD 2021 Diseases and Injuries Collaborators (2024). Global incidence, prevalence, years lived with disability (YLDs), disability-adjusted life-years (DALYs), and healthy life expectancy (HALE) for 371 diseases and injuries in 204 countries and territories and 811 subnational locations, 1990\u20132021: A systematic analysis for the Global Burden of Disease Study. Lancet, 403, 2133\u20132161."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1038\/s41584-022-00749-9","article-title":"Synovial inflammation in osteoarthritis progression","volume":"18","author":"Coras","year":"2022","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1186\/s13075-017-1229-9","article-title":"Synovitis in osteoarthritis: Current understanding with therapeutic implications","volume":"19","author":"Mathiessen","year":"2017","journal-title":"Arthritis Res. Ther."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.tvjl.2007.08.013","article-title":"The contribution of the synovium, synovial derived inflammatory cytokines and neuropeptides to the pathogenesis of osteoarthritis","volume":"179","author":"Sutton","year":"2009","journal-title":"Vet. J."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/j.bone.2012.02.012","article-title":"The role of synovitis in osteoarthritis pathogenesis","volume":"51","author":"Scanzello","year":"2012","journal-title":"Bone"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"5950","DOI":"10.1039\/C8FO01286E","article-title":"Anti-inflammatory effects of cinnamon extract and identification of active compounds influencing the TLR2 and TLR4 signaling pathways","volume":"9","author":"Schink","year":"2018","journal-title":"Food Funct."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Camacho, S., Michlig, S., de Senarclens-Bezen\u00e7on, C., Meylan, J., Meystre, J., Pezzoli, M., Markram, H., and le Coutre, J. (2015). Anti-obesity and anti-hyperglycemic effects of cinnamaldehyde via altered ghrelin secretion and functional impact on food intake and gastric emptying. Sci. Rep., 5.","DOI":"10.1038\/srep07919"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"5190603","DOI":"10.1155\/2020\/5190603","article-title":"Chemical composition and antioxidant, antimicrobial, and antiproliferative activities of Cinnamomum zeylanicum bark essential oil","volume":"2020","author":"Behbahani","year":"2020","journal-title":"Evid.-Based Complement. Altern. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e24120","DOI":"10.1016\/j.heliyon.2024.e24120","article-title":"Integrating network pharmacology and experimental verification to decipher the multitarget pharmacological mechanism of Cinnamomum zeylanicum essential oil in treating inflammation","volume":"10","author":"Mohanty","year":"2024","journal-title":"Heliyon"},{"key":"ref_11","unstructured":"GBD 2021 Osteoarthritis Collaborators (2023). Global, regional, and national burden of osteoarthritis, 1990\u20132020 and projections to 2050: A systematic analysis for the Global Burden of Disease Study. Lancet Rheumatol., 5, e508\u2013e522."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1136\/annrheumdis-2019-216515","article-title":"Global, regional and national burden of osteoarthritis 1990\u20132017: A systematic analysis of the Global Burden of Disease Study","volume":"79","author":"Safiri","year":"2020","journal-title":"Ann. Rheum. Dis."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Chou, C.-H., Jain, V., Gibson, J., Attarian, D.E., Haraden, C.A., Yohn, C.B., Laberge, R.-M., Gregory, S., and Kraus, V.B. (2020). Synovial cell cross-talk with cartilage plays a major role in the pathogenesis of osteoarthritis. Sci. Rep., 10.","DOI":"10.1038\/s41598-020-67730-y"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1186\/s13020-024-00899-w","article-title":"Natural products in osteoarthritis treatment: Bridging basic research to clinical applications","volume":"19","author":"Fang","year":"2024","journal-title":"Chin. Med."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Meckes-Fischer, M., and Nicasio-Torres, P. (2023). The journey of a medicinal plant throughout science: Sphaeralcea angustifolia (Cav.) G. Don (Malvaceae). Plants, 12.","DOI":"10.3390\/plants12020321"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1016\/j.phymed.2013.03.021","article-title":"Double-blind placebo-controlled trial of hydroxytyrosol of Olea europaea on pain in gonarthrosis","volume":"20","author":"Takeda","year":"2013","journal-title":"Phytomedicine"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e26542","DOI":"10.1097\/MD.0000000000026542","article-title":"Efficacy of GCWB106 (Chrysanthemum zawadskii var. latilobum extract) in osteoarthritis of the knee: A 12-week randomized, double-blind, placebo-controlled study","volume":"100","author":"Ha","year":"2021","journal-title":"Medicine"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Liu, L., Xu, L., Wang, S., Wang, L., Wang, X., Xu, H., Li, X., and Ye, H. (2022). Confirmation of inhibitingTLR4\/MyD88\/NF-\u03baB signalling pathway by Duhuo Jisheng decoction on Osteoarthritis: A network pharmacology approach-integrated experimental study. Front. Pharmacol., 12.","DOI":"10.3389\/fphar.2021.784822"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1016\/j.intimp.2011.12.009","article-title":"Inhibition of the NF-\u03baB signaling pathway by the curcumin analog, 3,5-Bis(2-pyridinylmethylidene)-4-piperidone (EF31): Anti-inflammatory and anti-cancer properties","volume":"12","author":"Olivera","year":"2012","journal-title":"Int. Immunopharmacol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"4","DOI":"10.15283\/ijsc23108","article-title":"Exosomes reshape the osteoarthritic defect: Emerging potential in regenerative medicine\u2014A review","volume":"17","author":"Sankaranarayanan","year":"2024","journal-title":"Int. J. Stem Cells"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Sankaranarayanan, J., Lee, S.C., Kim, H.K., Kang, J.Y., Kuppa, S.S., and Seon, J.K. (2024). Cinnamaldehyde-treated bone marrow mesenchymal-stem-cell-derived exosomes via aqueous two-phase system attenuate IL-1\u03b2-induced inflammation and catabolism via modulation of proinflammatory signaling pathways. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25137263"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Xia, T., Gao, R., Zhou, G., Liu, J., Li, J., and Shen, J. (2019). Trans-cinnamaldehyde inhibits IL-1\u03b2-stimulated inflammation in chondrocytes by suppressing NF-\u03baB and p38-JNK pathways and exerts chondrocyte protective effects in a rat model of osteoarthritis. BioMed Res. Int., 2019.","DOI":"10.1155\/2019\/4039472"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"5467342","DOI":"10.1155\/2023\/5467342","article-title":"Aqueous extract of Cinnamon (Cinnamomum spp.): Role in cancer and inflammation","volume":"2023","author":"Khedkar","year":"2023","journal-title":"Evid.-Based Complement. Altern. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1542\/peds.2012-3418","article-title":"Ingesting and aspirating dry cinnamon by children and adolescents: The \u201ccinnamon challenge\u201d","volume":"131","author":"Schaechter","year":"2013","journal-title":"Pediatrics"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"642942","DOI":"10.1155\/2014\/642942","article-title":"Cinnamon: A multifaceted medicinal plant","volume":"2014","author":"Rao","year":"2014","journal-title":"Evid.-Based Complement. Altern. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1311","DOI":"10.20959\/wjpr20175-8424","article-title":"Description of Darchini (Cinnamomum zeylanicum) in unani medicine: A review","volume":"13","author":"Shahabuddin","year":"2017","journal-title":"World J. Pharm. Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1111\/jcmm.17148","article-title":"Cinnamic Aldehyde, the main monomer component of Cinnamon, exhibits anti-inflammatory property in OA synovial fibroblasts via TLR4\/MyD88 pathway","volume":"26","author":"Chen","year":"2022","journal-title":"J. Cell. Mol. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1016\/j.fct.2007.07.016","article-title":"Cinnamaldehyde inhibits pro-inflammatory cytokines secretion from monocytes\/macrophages through suppression of intracellular signaling","volume":"46","author":"Chao","year":"2008","journal-title":"Food Chem. Toxicol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1208","DOI":"10.1038\/s41401-020-0359-9","article-title":"Cinnamaldehyde protects against rat intestinal ischemia\/reperfusion injuries by synergistic inhibition of NF-\u03baB and p","volume":"41","author":"Almoiliqy","year":"2020","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"106570","DOI":"10.1016\/j.intimp.2020.106570","article-title":"Cinnamaldehyde suppresses NLRP3 derived IL-1\u03b2 via activating succinate\/HIF-1 in rheumatoid arthritis rats","volume":"84","author":"Liu","year":"2020","journal-title":"Int. Immunopharmacol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1177\/19476035221114858","article-title":"Cinnamaldehyde induces the expression of MicroRNA-1285-5p and MicroRNA-140-5p in chondrocytes to ameliorate the apoptosis and inflammatory response","volume":"14","author":"Li","year":"2023","journal-title":"CARTILAGE"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Qureshi, K.A., Mohammed, S.A.A., Khan, O., Ali, H.M., El-Readi, M.Z., and Mohammed, H.A. (2022). Cinnamaldehyde-based self-nanoemulsion (CA-SNEDDS) accelerates wound healing and exerts antimicrobial, antioxidant, and anti-inflammatory effects in rats\u2019 skin burn model. Molecules, 27.","DOI":"10.3390\/molecules27165225"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e13285","DOI":"10.1111\/cpr.13285","article-title":"CircHIPK3 prevents chondrocyte apoptosis and cartilage degradation by sponging miR-30a-3p and promoting PON","volume":"55","author":"Shang","year":"2022","journal-title":"Cell Prolif"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1002\/jcp.22059","article-title":"TLR4-dependent induction of vascular adhesion molecule-1 in rheumatoid arthritis synovial fibroblasts: Roles of cytosolic phospholipase A2\u03b1\/cyclooxygenase","volume":"223","author":"Wu","year":"2010","journal-title":"J. Cell. Physiol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/23\/12914\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:43:47Z","timestamp":1760114627000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/23\/12914"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,30]]},"references-count":34,"journal-issue":{"issue":"23","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["ijms252312914"],"URL":"https:\/\/doi.org\/10.3390\/ijms252312914","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,30]]}}}