{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T16:26:44Z","timestamp":1784392004614,"version":"3.55.0"},"reference-count":45,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,4,12]],"date-time":"2026-04-12T00:00:00Z","timestamp":1775952000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100018684","name":"National Health Commission","doi-asserted-by":"publisher","award":["800000"],"award-info":[{"award-number":["800000"]}],"id":[{"id":"10.13039\/501100018684","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>This study aims to evaluate the therapeutic efficacy of emodin (EMO) in rheumatoid arthritis (RA) and to verify whether its underlying mechanism involves the blockade of pathological angiogenesis via the inhibition of the nuclear factor-kappa B (NF-\u03baB)\/hypoxia-inducible factor-1\u03b1 (HIF-1\u03b1)\/vascular endothelial growth factor (VEGF) signaling axis. Bovine type II collagen-induced arthritis (CIA) mouse models and lipopolysaccharide (LPS)-stimulated EA.hy926 endothelial cells were utilized in this study. The effects of EMO on joint pathological alterations, the expression of NF-\u03baB\/HIF-1\u03b1\/VEGF axis proteins, inflammatory cytokines (tumor necrosis factor-alpha (TNF-\u03b1), interleukin-6 (IL-6), and interleukin-1 beta (IL-1\u03b2)), and angiogenic capacity were assessed using histopathological analysis, Western blotting, immunohistochemistry (IHC), immunofluorescence, and tube formation assays. Furthermore, small interfering RNA (siRNA) interference targeting key molecules was employed to validate the molecular mechanisms underlying the therapeutic effects of EMO. In the CIA model group, the ankle joints of mice exhibited pronounced inflammatory infiltration, synovial hyperplasia, and bone destruction. Compared with the model group, both the EMO and methotrexate (MTX) treatment groups demonstrated attenuated synovial hyperplasia and cartilage destruction, along with significantly downregulated expression levels of key NF-\u03baB pathway proteins, HIF-1\u03b1, and VEGF in joint tissues (p &lt; 0.001). In vitro experiments revealed that EMO treatment significantly reduced the LPS-induced secretion of pro-inflammatory cytokines (TNF-\u03b1, IL-6, and IL-1\u03b2) (p &lt; 0.001), and decreased both the number and total length of tubular structures formed by endothelial cells compared to the control (p &lt; 0.001). Notably, siRNA-mediated knockdown of p65 resulted in decreased intracellular protein levels of HIF-1\u03b1 and VEGF, accompanied by a significant reduction in tube formation (p &lt; 0.001). This study demonstrates that EMO alleviates pathological damage in RA by inhibiting the activation of the NF-\u03baB signaling pathway, which subsequently downregulates pathological angiogenesis and inflammatory responses mediated by the HIF-1\u03b1\/VEGF axis. These findings provide a robust experimental basis for the potential application of EMO as a therapeutic agent for RA.<\/jats:p>","DOI":"10.3390\/ijms27083460","type":"journal-article","created":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T08:49:02Z","timestamp":1776070142000},"page":"3460","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Emodin Attenuates Rheumatoid Arthritis by Modulating the NF-\u03baB\/HIF-1\u03b1\/VEGF Signaling Pathway"],"prefix":"10.3390","volume":"27","author":[{"given":"Dehao","family":"Du","sequence":"first","affiliation":[{"name":"Department of Combination of Chinese and Western Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yihang","family":"Lou","sequence":"additional","affiliation":[{"name":"Institute of Literature in Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linlan","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Combination of Chinese and Western Medicine, 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 Combination of Chinese and Western Medicine, 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 Combination of Chinese and Western Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zexuan","family":"Qiu","sequence":"additional","affiliation":[{"name":"Department of Combination of Chinese and Western Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaofeng","family":"Rong","sequence":"additional","affiliation":[{"name":"Department of Combination of Chinese and Western Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,12]]},"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":"18001","DOI":"10.1038\/nrdp.2018.1","article-title":"Rheumatoid arthritis","volume":"4","author":"Smolen","year":"2018","journal-title":"Nat. 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