{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T13:14:41Z","timestamp":1789996481045,"version":"4.0.1"},"reference-count":47,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T00:00:00Z","timestamp":1789516800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background\/Objectives: Osteoarthritis (OA) is characterized by cartilage degeneration, extracellular matrix (ECM) disruption, inflammation, and impaired joint function. A standardized phytosterol-rich avocado\/soybean unsaponifiable preparation (CHL) was examined in monosodium iodoacetate (MIA)-induced OA in Sprague\u2013Dawley rats. Methods: Rats were orally administered low-, medium-, or high-dose CHL for 2 weeks before and 4 weeks after MIA induction. Results: CHL attenuated MIA-induced weight-bearing deficits and structural joint abnormalities. CHL also reduced cartilage degradation markers, including cartilage oligomeric matrix proteins and the C-terminal crosslinked telopeptide of type II collagen. CHL alleviated systemic inflammation by reducing serum interleukin-6, tumor necrosis factor-\u03b1, and prostaglandin E2 levels. Furthermore, CHL decreased the serum levels of matrix metalloproteinases (MMP)-1, MMP-2, MMP-9, and MMP-13, indicating reduced matrix-degrading responses. In joint cartilage tissues, CHL suppressed the mRNA expression of pro-inflammatory mediators and catabolic genes, such as Mmp1, Mmp3, and Mmp9. Additionally, CHL modulated cartilage anabolism and ECM-related markers by reducing collagen type I alpha 1 chain expression and enhancing SRY-box transcription factor 9, tissue inhibitor of metalloproteinase 1, and collagen type II alpha 1 chain expression. High-resolution liquid chromatography-mass spectrometry profiling of CHL revealed several tentatively identified compounds, such as (+)-discodermolide, epicoccamide, and brasilicardin C. Conclusions: Overall, these findings indicate that CHL may attenuate MIA-induced OA-associated functional impairment, structural alterations, inflammation, and cartilage matrix degradation, with medium doses showing the strongest protective effects. However, because CHL administration was initiated before OA induction, these findings primarily reflect preventive\/protective effects and may not directly represent the therapeutic efficacy of CHL in established OA.<\/jats:p>","DOI":"10.3390\/nu18183031","type":"journal-article","created":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T13:50:27Z","timestamp":1789566627000},"page":"3031","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["CHL Attenuates MIA-Induced Osteoarthritis by Regulating Inflammatory, Catabolic, and Anabolic Pathways Associated with Cartilage and Subchondral Bone Degeneration"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4571-515X","authenticated-orcid":false,"family":"Sanjay","sequence":"first","affiliation":[{"name":"Department of Food and Nutrition, College of BioNano Technology, Gachon University, Seongnam 13120, Gyeonggi-do, Republic of Korea"},{"name":"Institute for Aging and Clinical Nutrition Research, Gachon University, Seongnam 13120, Gyeonggi-do, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mi-Seon","family":"Woo","sequence":"additional","affiliation":[{"name":"R&D Center, Chong Kun Dang Healthcare Corp., Yongsan-gu, Seoul 04300, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"}]},{"given":"Jihee","family":"Yoo","sequence":"additional","affiliation":[{"name":"CH Labs Corp., Yeongdeungpo-gu, Seoul 07249, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"}]},{"given":"Tom","family":"Pfannenschmidt","sequence":"additional","affiliation":[{"name":"Innovation Management, K.-W. Pfannenschmidt GmbH, Habichthorst 36, 22459 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"data-curation","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8353-3619","authenticated-orcid":false,"given":"Hae-Jeung","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Food and Nutrition, College of BioNano Technology, Gachon University, Seongnam 13120, Gyeonggi-do, Republic of Korea"},{"name":"Institute for Aging and Clinical Nutrition Research, Gachon University, Seongnam 13120, Gyeonggi-do, Republic of Korea"},{"name":"Department of Health Sciences and Technology, Gachon Advanced Institute for Health Science and Technology (GAIHST), Gachon University, Incheon 21999, Republic of Korea"},{"name":"Gachon Biomedical Convergence Institute, Gachon University Gil Medical Center, Incheon 21565, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Xie, X., Zhang, K., Li, Y., Li, Y., Li, X., Lin, Y., Huang, L., and Tian, G. (2025). Global, regional, and national burden of osteoarthritis from 1990 to 2021 and projections to 2035: A cross-sectional study for the Global Burden of Disease Study 2021. PLoS ONE, 20.","DOI":"10.1371\/journal.pone.0324296"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1007\/s11914-015-0275-y","article-title":"Mechanisms and mediators that drive arthritis pain","volume":"13","author":"Krustev","year":"2015","journal-title":"Curr. Osteoporos. Rep."},{"key":"ref_3","first-page":"101010","article-title":"Revisiting osteoarthritis pathogenesis through the lens of cGAS-STING: Mitochondrial damage, pyroptosis, and inflammatory cascades","volume":"56","author":"Hu","year":"2025","journal-title":"J. Orthop. Transl."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"201","DOI":"10.3892\/etm.2024.12490","article-title":"Role of crosstalk between synovial cells and chondrocytes in osteoarthritis (Review)","volume":"27","author":"Chen","year":"2024","journal-title":"Exp. Ther. Med."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Batarfi, W.A., Yunus, M.H.M., Hamid, A.A., Maarof, M., and Abdul Rani, R. (2025). Breaking down osteoarthritis: Exploring inflammatory and mechanical signaling pathways. Life, 15.","DOI":"10.3390\/life15081238"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Peng, P., Zheng, W., Liu, Y., Huang, J., Zhang, B., Shen, J., and Cao, J. (2025). Imrecoxib attenuates osteoarthritis by modulating synovial macrophage polarization through inactivating COX-2\/PGE2 signaling pathway. Front. Bioeng. Biotechnol., 13.","DOI":"10.3389\/fbioe.2025.1526092"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Zhang, K., Wang, Z., He, J., Lu, L., Wang, W., Yang, A., Xie, H., Huang, L., Huang, Y., and Zhang, K. (2025). Mechanisms of synovial macrophage polarization in osteoarthritis pathogenesis and their therapeutic implications. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1637731"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1357","DOI":"10.1002\/art.21813","article-title":"Molecular mechanisms of cartilage destruction: Mechanics, inflammatory mediators, and aging collide","volume":"54","author":"Loeser","year":"2006","journal-title":"Arthritis Rheum."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1038\/s41413-025-00460-x","article-title":"The impact of mitochondrial dysfunction on osteoarthritis cartilage: Current insights and emerging mitochondria-targeted therapies","volume":"13","author":"Tan","year":"2025","journal-title":"Bone Res."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Ashruf, O.S., and Ansari, M.Y. (2022). Natural compounds: Potential therapeutics for the inhibition of cartilage matrix degradation in osteoarthritis. Life, 13.","DOI":"10.3390\/life13010102"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1016\/j.joca.2018.10.009","article-title":"Cartilage oligomeric matrix protein, C-terminal cross-linking telopeptide of type II collagen, and matrix metalloproteinase-3 as biomarkers for knee and hip osteoarthritis (OA) diagnosis: A systematic review and meta-analysis","volume":"27","author":"Hao","year":"2019","journal-title":"Osteoarthr. Cartil."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Fujii, Y., Liu, L., Yagasaki, L., Inotsume, M., Chiba, T., and Asahara, H. (2022). Cartilage homeostasis and osteoarthritis. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23116316"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1102S","DOI":"10.1177\/19476035211063858","article-title":"Role of mitochondria in physiology of chondrocytes and diseases of osteoarthritis and rheumatoid arthritis","volume":"13","author":"Kan","year":"2021","journal-title":"Cartilage"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"c7086","DOI":"10.1136\/bmj.c7086","article-title":"Cardiovascular safety of non-steroidal anti-inflammatory drugs: Network meta-analysis","volume":"342","author":"Trelle","year":"2011","journal-title":"BMJ"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"89","DOI":"10.12998\/wjcc.v3.i2.89","article-title":"State-of-the-art management of knee osteoarthritis","volume":"3","author":"Fibel","year":"2015","journal-title":"World J. Clin. Cases"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1177\/1947603514554992","article-title":"Management of osteoarthritis with avocado\/soybean unsaponifiables","volume":"6","author":"Christiansen","year":"2015","journal-title":"Cartilage"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Sabucedo-Su\u00e1rez, A., L\u00f3pez-Pe\u00f1a, M., Permuy, M., and Mu\u00f1\u00f3z, F. (2025). Soybean and avocado unsaponifiables: A review of their potential use in the treatment of osteoarthritis. Front. Vet. Sci., 11.","DOI":"10.3389\/fvets.2024.1473688"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Shen, M., Yuan, L., Zhang, J., Wang, X., Zhang, M., Li, H., Jing, Y., Zeng, F., and Xie, J. (2024). Phytosterols: Physiological functions and potential application. Foods, 13.","DOI":"10.3390\/foods13111754"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"116450","DOI":"10.1016\/j.intimp.2026.116450","article-title":"Daucosterol alleviates osteoarthritis by targeting chondrocyte senescence via inhibiting of the JNK pathway","volume":"175","author":"Chen","year":"2026","journal-title":"Int. Immunopharmacol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1249","DOI":"10.1016\/j.joca.2007.07.009","article-title":"Avocado soybean unsaponifiables (ASU) suppress TNF-\u03b1, IL-1\u03b2, COX-2, iNOS gene expression, and prostaglandin E2 and nitric oxide production in articular chondrocytes and monocyte\/macrophages","volume":"15","author":"Au","year":"2007","journal-title":"Osteoarthr. Cartil."},{"key":"ref_21","first-page":"1668","article-title":"Avocado\/soybean unsaponifiables prevent the inhibitory effect of osteoarthritic subchondral osteoblasts on aggrecan and type II collagen synthesis by chondrocytes","volume":"33","author":"Henrotin","year":"2006","journal-title":"J. Rheumatol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1016\/j.joca.2007.06.016","article-title":"Stress-induced signaling pathways in hyalin chondrocytes: Inhibition by avocado\u2013soybean unsaponifiables (ASU)","volume":"16","author":"Gabay","year":"2008","journal-title":"Osteoarthr. Cartil."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1002\/1529-0131(199801)41:1<81::AID-ART11>3.0.CO;2-9","article-title":"Symptomatic efficacy of avocado\/soybean unsaponifiables in the treatment of osteoarthritis of the knee and hip: A prospective, randomized, double-blind, placebo-controlled, multicenter clinical trial with a six-month treatment period and a two-month followup demonstrating a persistent effect","volume":"41","author":"Maheu","year":"1998","journal-title":"Arthritis Rheum."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1080\/030097401316909602","article-title":"Symptoms modifying effect of avocado\/soybean unsaponifiables (ASU) in knee osteoarthritis","volume":"30","author":"Appelboom","year":"2001","journal-title":"Scand. J. Rheumatol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1016\/j.joca.2007.10.003","article-title":"Symptomatic efficacy of avocado\u2013soybean unsaponifiables (ASU) in osteoarthritis (OA) patients: A meta-analysis of randomized controlled trials","volume":"16","author":"Christensen","year":"2008","journal-title":"Osteoarthr. Cartil."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1607","DOI":"10.1111\/1756-185X.13658","article-title":"Efficacy and safety of avocado-soybean unsaponifiables for the treatment of hip and knee osteoarthritis: A systematic review and meta-analysis of randomized placebo-controlled trials","volume":"22","year":"2019","journal-title":"Int. J. Rheum. Dis."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Lambert, C., Bellem\u00e8re, G., Boyer, G., Ponelle, F., Bauer, T., Legeny, M.C., Baudouin, C., and Henrotin, Y. (2022). Composition analysis and pharmacological activity of avocado\/soybean unsaponifiable products used in the treatment of osteoarthritis. Front. Pharmacol., 12.","DOI":"10.3389\/fphar.2021.781389"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.tice.2018.05.001","article-title":"Avocado soybean unsaponifiables ameliorates cartilage and subchondral bone degeneration in mono-iodoacetate-induced knee osteoarthritis in rats","volume":"52","year":"2018","journal-title":"Tissue Cell"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Goudarzi, R., Reid, A., and McDougall, J.J. (2018). Evaluation of the novel avocado\/soybean unsaponifiable Arthrocen to alter joint pain and inflammation in a rat model of osteoarthritis. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0191906"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"110471","DOI":"10.1016\/j.biopha.2020.110471","article-title":"Huoxuezhitong capsule ameliorates MIA-induced osteoarthritis of rats through suppressing PI3K\/Akt\/NF-\u03baB pathway","volume":"129","author":"Ju","year":"2020","journal-title":"BioMed Pharmacother."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1515\/biol-2020-0105","article-title":"CTRP9 protects against MIA-induced inflammation and knee cartilage damage by deactivating the MAPK\/NF-\u03baB pathway in rats with osteoarthritis","volume":"15","author":"Zheng","year":"2020","journal-title":"Open Life Sci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2261","DOI":"10.1007\/s10787-022-01060-5","article-title":"Anti-arthritic effects of Schisandra chinensis extract in monosodium iodoacetate-induced osteoarthritis rats","volume":"30","author":"Lee","year":"2022","journal-title":"Inflammopharmacology"},{"key":"ref_33","unstructured":"Thermo Fisher Scientific (2026, August 12). mzCloud: High Resolution Mass Spectral Database. Available online: https:\/\/www.mzcloud.org."},{"key":"ref_34","unstructured":"Thermo Fisher Scientific (2026, August 12). mzVault Software and Local Spectral Library. Available online: https:\/\/www.thermofisher.com\/us\/en\/home\/industrial\/mass-spectrometry\/liquid-chromatography-mass-spectrometry-lc-ms\/lc-ms-software\/mass-spectral-libraries.html."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"7842","DOI":"10.1039\/D0FO00992J","article-title":"Cissus quadrangularis (veldt grape) attenuates disease progression and anatomical changes in mono sodium iodoacetate (MIA)-induced knee osteoarthritis in the rat model","volume":"11","author":"Lakshmanan","year":"2020","journal-title":"Food Funct."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"8565132","DOI":"10.1155\/2018\/8565132","article-title":"Antiosteoarthritic effects of ChondroT in a rat model of monosodium iodoacetate-induced osteoarthritis","volume":"2018","author":"Bae","year":"2018","journal-title":"Evid. Based Complement. Altern. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1016\/j.jep.2014.05.023","article-title":"Anti-arthritic activity of Xanthium strumarium L. extract on complete Freund\u2019s adjuvant induced arthritis in rats","volume":"155","author":"Lin","year":"2014","journal-title":"J. Ethnopharmacol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1080\/15476910601115184","article-title":"Protective effect of ethanolic extract of seeds of Moringa oleifera Lam. against inflammation associated with development of arthritis in rats","volume":"4","author":"Mahajan","year":"2007","journal-title":"J. Immunotoxicol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1196","DOI":"10.1124\/mol.59.5.1196","article-title":"Tripterygium wilfordii Hook F extract suppresses proinflammatory cytokine-induced expression of matrix metalloproteinase genes in articular chondrocytes by inhibiting activating protein-1 and nuclear factor-\u03baB activities","volume":"59","author":"Sylvester","year":"2001","journal-title":"Mol. Pharmacol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1007\/s10616-019-00298-2","article-title":"Stichopus chloronotus aqueous extract as a chondroprotective agent for human chondrocytes isolated from osteoarthitis articular cartilage in vitro","volume":"71","author":"Chua","year":"2019","journal-title":"Cytotechnology"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"537","DOI":"10.4162\/nrp.2025.19.4.537","article-title":"Anti-osteoarthritis effect of a standardized Curcuma longa extract in monosodium iodoacetate-induced osteoarthritis rats","volume":"19","author":"Lee","year":"2025","journal-title":"Nutr. Res. Pract."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1093\/intimm\/dxz044","article-title":"The leukotriene receptors as therapeutic targets of inflammatory diseases","volume":"31","author":"Sasaki","year":"2019","journal-title":"Int. Immunol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1093\/cvr\/cvn277","article-title":"Leukotriene B4 enhances the activity of nuclear factor-\u03baB pathway through BLT1 and BLT2 receptors in atherosclerosis","volume":"81","author":"Vidal","year":"2009","journal-title":"Cardiovasc. Res."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Byun, J.-H., Choi, C.-W., Jang, M.-J., Lim, S.H., Han, H.J., and Choung, S.-Y. (2020). Anti-osteoarthritic mechanisms of Chrysanthemum zawadskii var. latilobum in MIA-induced osteoarthritic rats and interleukin-1\u03b2-induced SW1353 human chondrocytes. Medicina, 56.","DOI":"10.3390\/medicina56120685"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1080\/08923973.2019.1641723","article-title":"Isorhamnetin ameliorates inflammatory responses and articular cartilage damage in the rats of monosodium iodoacetate-induced osteoarthritis","volume":"41","author":"Tsai","year":"2019","journal-title":"Immunopharmacol. Immunotoxicol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"147","DOI":"10.11005\/jbm.2017.24.3.147","article-title":"Regulation of cartilage development and diseases by transcription factors","volume":"24","author":"Nishimura","year":"2017","journal-title":"J. Bone Metab."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Choudhary, D., Kothari, P., Tripathi, A.K., Singh, S., Adhikary, S., Ahmad, N., Kumar, S., Dev, K., Mishra, V.K., and Shukla, S. (2018). Spinacia oleracea extract attenuates disease progression and sub-chondral bone changes in monosodium iodoacetate-induced osteoarthritis in rats. BMC Complement. Altern. Med., 18.","DOI":"10.1186\/s12906-018-2117-9"}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/18\/18\/3031\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T12:51:42Z","timestamp":1789995102000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/18\/18\/3031"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,16]]},"references-count":47,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["nu18183031"],"URL":"https:\/\/doi.org\/10.3390\/nu18183031","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,16]]}}}