{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T02:02:28Z","timestamp":1790301748297,"version":"4.1.0"},"reference-count":59,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,12,25]],"date-time":"2025-12-25T00:00:00Z","timestamp":1766620800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Integrated Traditional Chinese and Western Medicine Key Department Construction Project","award":["[2025]264"],"award-info":[{"award-number":["[2025]264"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["81973661"],"award-info":[{"award-number":["81973661"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82104828"],"award-info":[{"award-number":["82104828"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Xingliao Talent Program Medical Experts Project","award":["YXMJ-MZY-12"],"award-info":[{"award-number":["YXMJ-MZY-12"]}]},{"name":"Xingliao Talent Program Medical Experts Project","award":["YXMJ-QNMZY-10"],"award-info":[{"award-number":["YXMJ-QNMZY-10"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background: Rheumatoid arthritis (RA) is a chronic and debilitating autoimmune disease with a complex etiology, creating a significant unmet clinical need for safer and more effective therapeutics. Coix seed oil (CSO), a traditional Chinese medicine with a long history of use against RA, represents a promising candidate; however, its precise mechanisms of action remain largely unexplored. Objectives: This study aimed to elucidate the mechanistic basis for the anti-arthritic effects of CSO, with a specific focus on its role in modulating the gut-joint axis. Methods: A collagen-induced arthritis (CIA) rat model was employed. The therapeutic efficacy of CSO was evaluated through detailed assessments of arthritic symptoms, joint histopathology, and Micro-CT analysis. To unravel the mechanism, an integrative multi-omics approach was applied, combining untargeted fecal metabolomics with targeted serum metabolomics, which pinpointed butyric acid as a key differential metabolite. This was integrated with 16S rRNA sequencing to profile gut microbiota remodeling. The causal role of butyrate was further verified by exogenous sodium butyrate supplementation in CIA mice. Finally, network pharmacology predictions of potential effector proteins were experimentally validated in vivo using immunofluorescence and qPCR. Results: CSO treatment significantly alleviated joint swelling and bone damage in CIA rats after the treatment of 7 days, especially on day 35. CSO primarily restored gut dysbiosis in the CIA model by upregulating butyrate levels, increasing four butyrate-producing probiotics at the genus level, and reducing two pathogenic bacteria. Further exogenous butyrate supplementation validated its ability to improve RA phenotypes. Network pharmacology analysis speculated that there were 142 common targets between CSO and RA, among which NLRP3 was its potential effector protein. In vivo studies verified the suppression of NLRP3 inflammasome activation and reduced expression of subsequent inflammatory mediators by CSO. Conclusions: Coix Seed Oil alleviates RA by orchestrating a dual-mechanism action, it remodels the gut microbiota to enhance the production of the microbiotic metabolite butyrate, while also inhibiting the NLRP3 inflammasome pathway. These findings collectively elucidate that CSO mediates its anti-arthritic effects through a novel \u201cgut-butyrate-joint\u201d axis, underscoring its potential as a promising dietary supplement or therapeutic agent derived from medicine-food homology for the management of RA.<\/jats:p>","DOI":"10.3390\/ph19010048","type":"journal-article","created":{"date-parts":[[2025,12,26]],"date-time":"2025-12-26T02:07:58Z","timestamp":1766714878000},"page":"48","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Integrative Multi-Omics Elucidates the Therapeutic Effect of Coix Seed Oil on Rheumatoid Arthritis via the Gut-Butyrate-Joint Axis and NLRP3 Inflammasome Suppression"],"prefix":"10.3390","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5972-8552","authenticated-orcid":false,"given":"Fanxin","family":"Ouyang","sequence":"first","affiliation":[{"name":"National Regional Diagnosis and Treatment Center for TCM Rheumatology, The First Hospital of China Medical University, China Medical University, Shenyang 110001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-6978-8064","authenticated-orcid":false,"given":"Xiaoyu","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Traditional Chinese Medicine, Liaoning University of Traditional Chinese Medicine, Shenyang 110847, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-4707-5937","authenticated-orcid":false,"given":"Rui","family":"Miao","sequence":"additional","affiliation":[{"name":"School of Traditional Chinese Medicine, Liaoning University of Traditional Chinese Medicine, Shenyang 110847, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongxi","family":"Kong","sequence":"additional","affiliation":[{"name":"National Regional Diagnosis and Treatment Center for TCM Rheumatology, The First Hospital of China Medical University, China Medical University, Shenyang 110001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenxin","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Traditional Chinese Medicine, Liaoning University of Traditional Chinese Medicine, Shenyang 110847, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhidan","family":"Wang","sequence":"additional","affiliation":[{"name":"National Regional Diagnosis and Treatment Center for TCM Rheumatology, The First Hospital of China Medical University, China Medical University, Shenyang 110001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xu","family":"Han","sequence":"additional","affiliation":[{"name":"National Regional Diagnosis and Treatment Center for TCM Rheumatology, The First Hospital of China Medical University, China Medical University, Shenyang 110001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuang","family":"Ren","sequence":"additional","affiliation":[{"name":"National Regional Diagnosis and Treatment Center for TCM Rheumatology, The First Hospital of China Medical University, China Medical University, Shenyang 110001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2972-3870","authenticated-orcid":false,"given":"Jie","family":"Zhang","sequence":"additional","affiliation":[{"name":"National Regional Diagnosis and Treatment Center for TCM Rheumatology, The First Hospital of China Medical University, China Medical University, Shenyang 110001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fanyan","family":"Meng","sequence":"additional","affiliation":[{"name":"National Regional Diagnosis and Treatment Center for TCM Rheumatology, The First Hospital of China Medical University, China Medical University, Shenyang 110001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2019","DOI":"10.1016\/S0140-6736(23)01525-8","article-title":"Rheumatoid Arthritis","volume":"402","author":"Bathon","year":"2023","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e509","DOI":"10.1002\/mco2.509","article-title":"Rheumatoid Arthritis: Pathogenesis and Therapeutic Advances","volume":"5","author":"Gao","year":"2024","journal-title":"MedComm"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Zhao, J., Guo, S., Schrodi, S.J., and He, D. 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