{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T20:54:21Z","timestamp":1792097661993,"version":"4.4.0"},"reference-count":26,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,6,25]],"date-time":"2025-06-25T00:00:00Z","timestamp":1750809600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Health Commission Flagship Project for Integrated Traditional Chinese and Western Medicine Department Development","award":["221"],"award-info":[{"award-number":["221"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CIMB"],"abstract":"<jats:p>In this study, we investigated the inhibitory effects of emodin on pyroptosis in rheumatoid arthritis (RA) synovial cells by modulating the HIF-1\u03b1\/NLRP3 inflammasome pathway and mitochondrial autophagy. By employing a chemically induced hypoxia model with CoCl2, we established experimental groups including normal control, model group, and emodin-treated groups at different concentrations (5 \u03bcM, 10 \u03bcM, and 20 \u03bcM). We optimized the CoCl2 concentration via CCK-8 assay to ensure cell viability. ELISA, Western blotting, transmission electron microscopy, and immunofluorescence were employed to assess HIF-1\u03b1, IL-1\u03b2, and IL-18 levels, pyroptosis-related proteins, autophagy markers, and NLRP3 fluorescence intensity. Statistical analysis revealed that increased CoCl2 concentrations led to a significant cell viability reduction (p &lt; 0.05), with 300 \u03bcM CoCl2 causing ~50% inhibition at 24 h. Transmission electron microscopy confirmed autophagosome formation in emodin-treated groups, while Western blotting showed dose-dependent downregulation of HIF-1\u03b1, NLRP3, BNIP3, and related proteins. Immunofluorescence revealed reduced NLRP3 fluorescence intensity with increasing emodin doses (p &lt; 0.05), alongside dose-dependent cell viability recovery (p &lt; 0.05). Our findings demonstrate that emodin alleviates RA synovitis through dual mechanisms: inhibition of mitochondrial autophagy to regulate the balance between mitochondrial autophagy and pyroptosis, and suppression of HIF-1\u03b1\/NLRP3-mediated pyroptosis signaling, thereby reducing IL-1\u03b2 and IL-18 release and inhibiting synovial cell proliferation. This study provides innovative approaches for targeted RA therapy.<\/jats:p>","DOI":"10.3390\/cimb47070486","type":"journal-article","created":{"date-parts":[[2025,6,26]],"date-time":"2025-06-26T05:53:13Z","timestamp":1750917193000},"page":"486","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Investigating the Mechanism of Emodin in Rheumatoid Arthritis Through the HIF-1\u03b1\/NLRP3 Pathway and Mitochondrial Autophagy"],"prefix":"10.3390","volume":"47","author":[{"given":"Dehao","family":"Du","sequence":"first","affiliation":[{"name":"Department of Integrated Traditional Chinese and Western Medicine, Sci-Tech Innovation Center, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linlan","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Integrated Traditional Chinese and Western Medicine, Sci-Tech Innovation Center, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayu","family":"Tian","sequence":"additional","affiliation":[{"name":"Department of Integrated Traditional Chinese and Western Medicine, Sci-Tech Innovation Center, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lianying","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Integrated Traditional Chinese and Western Medicine, Sci-Tech Innovation Center, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences, Chongqing Medical University, Chongqing 400016, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yifu","family":"Tang","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences, Chongqing Medical University, Chongqing 400016, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zexuan","family":"Qiu","sequence":"additional","affiliation":[{"name":"Department of Integrated Traditional Chinese and Western Medicine, Sci-Tech Innovation Center, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingdan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Integrated Traditional Chinese and Western Medicine, Sci-Tech Innovation Center, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9549-8099","authenticated-orcid":false,"given":"Xiaofeng","family":"Rong","sequence":"additional","affiliation":[{"name":"Department of Integrated Traditional Chinese and Western Medicine, Sci-Tech Innovation Center, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1360","DOI":"10.1001\/jama.2018.13103","article-title":"Diagnosis and management of rheumatoid arthritis: A review","volume":"320","author":"Aletaha","year":"2018","journal-title":"JAMA"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2023","DOI":"10.1016\/S0140-6736(16)30173-8","article-title":"Rheumatoid arthritis","volume":"388","author":"Smolen","year":"2016","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Miao, H.B., Wang, F., Lin, S., and Chen, Z. 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