{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T09:03:49Z","timestamp":1784538229898,"version":"3.55.0"},"reference-count":45,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,7,19]],"date-time":"2026-07-19T00:00:00Z","timestamp":1784419200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Postgraduate Research & Practice Innovation Program of Jiangsu Province","award":["KYCX24_0689"],"award-info":[{"award-number":["KYCX24_0689"]}]},{"name":"Horizontal Research Projects","award":["BYH2026036"],"award-info":[{"award-number":["BYH2026036"]}]},{"name":"Horizontal Research Projects","award":["BYH202314"],"award-info":[{"award-number":["BYH202314"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>Background: Osteoarthritis (OA) pathogenesis involves inflammatory-metabolic crosstalk driving cartilage destruction, yet the mechanisms of potential therapeutics like curcumin remain poorly defined. Methods: We integrated untargeted metabolomics, transcriptomic analysis of four GEO datasets (GSE12021, GSE55235, GSE55457, GSE82107), and three machine learning algorithms (LASSO, Random Forest, XGBoost) to characterize curcumin\u2019s effects on IL-1\u03b2-induced human chondrocytes. Results: Metabolomic profiling demonstrated that IL-1\u03b2 caused significant depletion of TCA cycle intermediates compared to blank controls, including pyruvate (log2FC = \u22121.34, p &lt; 0.001) and malate (log2FC = \u22120.54, p &lt; 0.001). High-dose curcumin (10 \u03bcM) significantly restored these metabolites towards normal levels (pyruvate log2FC = \u22120.01 vs. model; malate log2FC = \u22120.20 vs. model). Three machine learning algorithms converged on a six-gene inflammatory-metabolic signature (NFKBIA, MMP9, LCK, TDO2, HADHA, VEGFA), all showing excellent discriminative performance for OA (individual AUCs &gt; 0.75). qRT-PCR validation confirmed that high-dose curcumin significantly downregulated pro-inflammatory genes compared to IL-1\u03b2 treatment alone: JUN (log2FC = \u22120.68, p &lt; 0.001), IL6 (log2FC = \u22121.13, p &lt; 0.001), PTGS2 (log2FC = \u22120.94, p &lt; 0.001), CCL20 (log2FC = \u22121.51, p &lt; 0.001), and MMP9 (log2FC = \u22120.42, p &lt; 0.001). Conversely, curcumin significantly upregulated the NF-\u03baB inhibitor NFKBIA (log2FC = 0.40, p &lt; 0.001), whose expression was initially suppressed by IL-1\u03b2 (\u2212log2FC = 0.76 vs. blank, p &lt; 0.001). Conclusions: This systems-level analysis suggests curcumin modulates metabolic-inflammatory networks in OA chondrocytes, with NFKBIA as a candidate mediator, offering a mechanistic framework for drug-like molecule development despite curcumin\u2019s own translational limitations.<\/jats:p>","DOI":"10.3390\/metabo16070506","type":"journal-article","created":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T07:54:13Z","timestamp":1784534053000},"page":"506","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Restoring Metabolic-Inflammatory Homeostasis: Curcumin\u2019s Multi-Layered Defense Against Chondrocyte Dysfunction"],"prefix":"10.3390","volume":"16","author":[{"given":"Cong","family":"Wang","sequence":"first","affiliation":[{"name":"School of Chinese Medicine, Bozhou University, Bozhou 236800, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanran","family":"Li","sequence":"additional","affiliation":[{"name":"School of Chinese Medicine, Bozhou University, Bozhou 236800, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huihui","family":"Meng","sequence":"additional","affiliation":[{"name":"School of Chinese Medicine, Bozhou University, Bozhou 236800, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaocheng","family":"Shi","sequence":"additional","affiliation":[{"name":"School of Chinese Medicine, Bozhou University, Bozhou 236800, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yifan","family":"Sun","sequence":"additional","affiliation":[{"name":"School of Chinese Medicine, Bozhou University, Bozhou 236800, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ke","family":"Che","sequence":"additional","affiliation":[{"name":"School of Chinese Medicine, Bozhou University, Bozhou 236800, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Yu","sequence":"additional","affiliation":[{"name":"School of Chinese Medicine, Bozhou University, Bozhou 236800, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,19]]},"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 Osteoarthritis Collaborators (2023). 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