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Cyclic nitroxide radicals exhibit diverse biological activities, but their effects on liver fibrosis remain unclear. This study systematically evaluates the therapeutic potential of 3-carbamoyl proxyl nitroxide (3-CP) against carbon tetrachloride (CCl\u2084)-induced liver fibrosis. In vitro, 3-CP inhibited hepatic stellate cell (HSC) activation, migration, and proliferation, and reduced \u03b1-smooth muscle actin (\u03b1-SMA) and collagen I (COL1) expression. In a BALB\/c mouse model of CCl4-induced liver fibrosis, 20 and 40\u00a0mg\/kg 3-CP reduced the fibrosis area from 13.6\u2009\u00b1\u20091.0% (model group) to 6.9\u2009\u00b1\u20090.9% and 5.7\u2009\u00b1\u20091.3%, respectively, accompanied by decreased serum transaminase levels, restored liver architecture, and diminished collagen deposition. Mechanistic studies revealed that 3-CP modulated the TLR4\/NF-\u03baB signaling pathway, downregulating phosphorylated NF-\u03baB p65 (p-p65) and reducing hepatic mRNA levels of pro-inflammatory (IL-1\u03b2, IL-6, TNF-\u03b1) and pro-fibrotic (TGF-\u03b2) cytokines by approximately 35\u201355%. Supportive in silico analysis suggested potential interactions between 3-CP and key pathway proteins (TLR4, MyD88, IKK\u03b2, p65, I\u03baB\u03b1). These findings indicate that 3-CP represents a promising therapeutic candidate that concurrently addresses oxidative damage and inflammatory signaling during liver fibrogenesis.<\/jats:p>","DOI":"10.1038\/s41598-026-46137-1","type":"journal-article","created":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T23:15:47Z","timestamp":1774653347000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["3-carbamoyl proxyl nitroxide attenuates CCl4-induced liver fibrosis in mice through antioxidant-inflammatory regulation of TLR4\/NF-\u03baB signaling pathway"],"prefix":"10.1038","volume":"16","author":[{"given":"Ru","family":"Yao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rong","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yujie","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Panpan","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fangbin","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongfang","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,3,27]]},"reference":[{"key":"46137_CR1","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1172\/jci88881","volume":"127","author":"Y Koyama","year":"2017","unstructured":"Koyama, Y. & Brenner, D. 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