{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T21:29:55Z","timestamp":1773091795171,"version":"3.50.1"},"reference-count":27,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T00:00:00Z","timestamp":1773014400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Joint Project of Liaoning Provincial Science and Technology Program \u201cGermplasm Resource Innovation and New Variety Promotion and Demonstration of Taxus cuspidata\u201d","award":["2024JH2\/102600132"],"award-info":[{"award-number":["2024JH2\/102600132"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>This study aimed to investigate the effect and underlying mechanism of Taxus cuspidata seed oil (TCSO) on carbon tetrachloride (CCl4)-induced hepatic fibrosis in mice. A mouse model of hepatic fibrosis was established by CCl4 induction, and the model mice were subsequently treated orally with high dose or low dose TCSO for eight weeks. The degree of liver fibrosis and the mechanism of action were assessed through organ indices, serum biochemical markers, oxidative stress levels, histopathological examination, and molecular biological analyses. The results demonstrated that TCSO significantly reduced serum levels of alanine transaminase (ALT), aspartate transaminase (AST), and alkaline phosphatase (ALP). Concurrently, it decreased the concentrations of liver fibrosis markers, including procollagen III (PC III), collagen IV (IV-C), hyaluronic acid (HA), and laminin (LN), and reduced hepatic collagen deposition. Furthermore, TCSO enhanced the activities of the antioxidants superoxide dismutase (SOD) and glutathione (GSH) while inhibiting the production of the lipid peroxidation product malondialdehyde (MDA), and it ameliorated histopathological alterations in liver tissue. Additionally, TCSO markedly downregulated the expression of key fibrogenic proteins, such as transforming growth factor-\u03b21 (TGF-\u03b21), matrix metalloproteinase-2 (MMP-2), and tissue inhibitor of metalloproteinases-1 (TIMP-1), thereby effectively suppressing the progression of hepatic fibrosis. In conclusion, TCSO ameliorates hepatic fibrosis in mice by reducing hepatotoxic enzyme activity and collagen deposition, enhancing antioxidant capacity, and downregulating the expression of fibrosis-related proteins.<\/jats:p>","DOI":"10.3390\/biology15050442","type":"journal-article","created":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T11:06:52Z","timestamp":1773054412000},"page":"442","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Protective Effects and Mechanisms of Taxus cuspidata Seed Oil on CCl4-Induced Hepatic Fibrosis in Mice"],"prefix":"10.3390","volume":"15","author":[{"given":"Li","family":"Gao","sequence":"first","affiliation":[{"name":"School of Agriculture, Liaodong University, Dandong 118003, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hui","family":"Tian","sequence":"additional","affiliation":[{"name":"School of Agriculture, Liaodong University, Dandong 118003, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiangli","family":"Bai","sequence":"additional","affiliation":[{"name":"School of Agriculture, Liaodong University, Dandong 118003, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanwen","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Agriculture, Liaodong University, Dandong 118003, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1002\/hep.29803","article-title":"Hepatic stellate cell derived platelet derived growth factor receptor alpha enriched extracellular vesicles promote liver fibrosis in mice through SHP2","volume":"68","author":"Kostallari","year":"2018","journal-title":"Hepatology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"5115","DOI":"10.1039\/C9FO01010F","article-title":"Protective effects of trans 2,3,5,4\u2032-tetrahydroxystilbene 2-O-beta-D-glucopyranoside on liver fibrosis and renal injury induced by CCl4 via down-regulating p-ERK1\/2 and p-Smad1\/2","volume":"10","author":"Long","year":"2019","journal-title":"Food Funct."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"105","DOI":"10.4137\/BMI.S10009","article-title":"Molecular serum markers of liver fibrosis","volume":"7","author":"Liu","year":"2012","journal-title":"Biomark. Insights"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.phymed.2017.07.005","article-title":"Hepatoprotective effects of Yulangsan flavone against carbon tetrachloride (CCl4)-induced hepatic fibrosis in rats","volume":"33","author":"Guo","year":"2017","journal-title":"Phytomedicine"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1704","DOI":"10.1136\/gutjnl-2016-313392","article-title":"The HLF\/IL-6\/STAT3 feedforward circuit drives hepatic stellate cell activation to promote liver fibrosis","volume":"67","author":"Xiang","year":"2018","journal-title":"Gut"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1038\/s41563-019-0546-6","article-title":"Taxanes convert regions of perturbed microtubule growth into rescue sites","volume":"19","author":"Rai","year":"2020","journal-title":"Nat. Mater."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1007\/s00280-015-2893-6","article-title":"Treatment regimens of classical and newer taxanes","volume":"77","author":"Joerger","year":"2016","journal-title":"Cancer Chemother. Pharmacol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/j.lfs.2018.09.037","article-title":"Paclitaxel alleviates liver fibrosis induced by bile duct ligation in rats: Role of TGF-\u03b21, IL-10 and c-Myc","volume":"211","author":"Sharawy","year":"2018","journal-title":"Life Sci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/j.jss.2006.12.558","article-title":"Paclitaxel interrupts TGF-beta1 signaling between gallbladder epithelial cells and myofibroblasts","volume":"141","author":"Choi","year":"2007","journal-title":"J. Surg. Res."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Yu, J.H. (2012). Studies on the isolation and purification of polyprenols from Taxus chinensis var. mairei and its antifibrotic effect. [Ph.D. Thesis, Zhejiang University].","DOI":"10.1016\/j.fitote.2012.01.007"},{"key":"ref_11","first-page":"395","article-title":"Therapeutic effects of polyprenols from pine needles on liver fibrosis induced by chronic immune liver injury in rats","volume":"24","author":"Zheng","year":"2013","journal-title":"Lishizhen Med. Mater. Medica Res."},{"key":"ref_12","first-page":"392","article-title":"Analysis of chemical composition in the seed of Taxus chinensis var. mairei","volume":"8","author":"Huang","year":"2002","journal-title":"Chin. J. Appl. Environ. Biol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"107910","DOI":"10.1016\/j.fbio.2025.107910","article-title":"Sciadonic acid rich Torreya grandis oil improves hepatic steatosis via PPAR\u03b1 activation and arachidonic-acid remodeling","volume":"74","author":"Zhang","year":"2025","journal-title":"Food Biosci."},{"key":"ref_14","first-page":"298","article-title":"Nutritional Components of Taxus chinensis var. mairei Seeds and Acute Toxicity of Its Aril","volume":"33","author":"Tang","year":"2012","journal-title":"Food Sci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"4205","DOI":"10.29219\/fnr.v64.4205","article-title":"Hepatoprotective effect of oil from Cornus wilsoniana fruits against carbon tetrachloride-induced hepatic fibrosis in mice","volume":"64","author":"Liu","year":"2020","journal-title":"Food Nutr. Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.nut.2017.12.011","article-title":"Camelia oil and soybean-camelia oil blend enhance antioxidant activity and cardiovascular protection in hamsters","volume":"51\u201352","author":"Chou","year":"2018","journal-title":"Nutrition"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"830","DOI":"10.1136\/gutjnl-2014-306842","article-title":"Pathobiology of liver fibrosis: A translational success story","volume":"64","author":"Lee","year":"2015","journal-title":"Gut."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"4582","DOI":"10.1039\/C9FO02258A","article-title":"Camellia oil (Camellia oleifera Abel.) attenuates CCl4-induced liver fibrosis via suppressing hepatocyte apoptosis in mice","volume":"11","author":"Lei","year":"2020","journal-title":"Food Funct."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2327","DOI":"10.1002\/jsfa.8042","article-title":"Pomegranate juice prevents development of non-alcoholic fatty liver disease in rats by attenuating oxidative stress and inflammation","volume":"97","author":"Noori","year":"2017","journal-title":"J. Sci. Food Agric."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1007\/s00394-018-1718-x","article-title":"Gut-derived lipopolysaccharides increase post-prandial oxidative stress via Nox2 activation in patients with impaired fasting glucose tolerance: Effect of extra-virgin olive oil","volume":"58","author":"Carnevale","year":"2019","journal-title":"Eur. J. Nutr."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1002\/hep.510310114","article-title":"Expression and activation of pro-MMP-2 and pro-MMP-9 during rat liver regeneration","volume":"31","author":"Kim","year":"2000","journal-title":"Hepatology"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/S0009-8981(01)00730-6","article-title":"Diagnostic potential of circulating TIMP-1 and MMP-2 as markers of liver fibrosis in patients with chronic hepatitis C","volume":"316","author":"Boeker","year":"2002","journal-title":"Clin. Chim. Acta."},{"key":"ref_23","first-page":"736421","article-title":"Flaxseed oil attenuates hepatic inflammation and fibrosis induced by high-carbohydrate diet in Nile tilapia by regulating liver n-3 PUFA levels and fatty acid composition","volume":"536","author":"Zhang","year":"2021","journal-title":"Aquaculture"},{"key":"ref_24","first-page":"1984","article-title":"Omega-3 polyunsaturated fatty acids attenuate non-alcoholic steatohepatitis-induced fibrosis through inhibition of betacellulin in mice","volume":"6","author":"Liu","year":"2022","journal-title":"Hepatol. Commun."},{"key":"ref_25","first-page":"114456","article-title":"Olive oil and flaxseed oil nanoemulsion with ginger extract alleviates CCl4-induced liver fibrosis in rats via modulation of oxidative stress and TGF-\u03b2\/MMP9 signaling pathway","volume":"185","year":"2024","journal-title":"Food Chem. Toxicol."},{"key":"ref_26","unstructured":"Mastaloudis, A., Wood, S.M., Hester, S.N., Bartolome, A., and Packer, L. (2022). Wheat germ oil vitamin E protects against lipotoxicity in human hepatoma cells: A transcriptomic analysis reveals distinct gene expression patterns compared to pure \u03b1-tocopherol. Nutrients, 14."},{"key":"ref_27","first-page":"1658","article-title":"Dietary long-chain saturated fatty acids accelerate MASH-related fibrosis progression compared to medium-chain fatty acids: A comparative study of cocoa butter and coconut oil","volume":"77","author":"Wang","year":"2023","journal-title":"Hepatology"}],"container-title":["Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-7737\/15\/5\/442\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T11:36:34Z","timestamp":1773056194000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-7737\/15\/5\/442"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,9]]},"references-count":27,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2026,3]]}},"alternative-id":["biology15050442"],"URL":"https:\/\/doi.org\/10.3390\/biology15050442","relation":{},"ISSN":["2079-7737"],"issn-type":[{"value":"2079-7737","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,9]]}}}