{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T19:17:38Z","timestamp":1788290258778,"version":"build-2803163510"},"reference-count":44,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T00:00:00Z","timestamp":1762128000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Science and Technology Program of Guangzhou, China","award":["202002020006"],"award-info":[{"award-number":["202002020006"]}]},{"DOI":"10.13039\/501100012166","name":"National Key R&D Program of China","doi-asserted-by":"crossref","award":["2017YFC1703102"],"award-info":[{"award-number":["2017YFC1703102"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Science and Technology Program of Bijie","award":["[2022]2"],"award-info":[{"award-number":["[2022]2"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background: Cili (Rosa roxburghii Tratt) is a unique fruit native to China\u2019s Yunnan\u2013Guizhou Plateau, rich in vitamin C, polyphenols, and triterpene, with broad health-promoting effects. Although cili\u2019s hepatoprotective properties are reported, the bioactive components and underlying mechanisms remain poorly defined. Methods: We enriched proanthocyanidins from cili using column chromatography, identified their components via UPLC-Q-TOF-MS\/MS, and validated their anti-liver fibrosis effects through in vitro and in vivo experiments. Results: Herein, we developed a novel proanthocyanidin-rich cili fruit extract (PACs-CFE) containing 84.2% total proanthocyanidins, comprising catechins, epicatechins, and diverse B-type dimers, trimers, tetramers, and gallate esters, as characterized by UPLC-Q-TOF-MS\/MS. PACs-CFE inhibited LX-2 activation, suppressed collagen III and \u03b1-SMA expression, and induced ferroptosis via mitochondrial injury, reactive oxygen species accumulation, and GPX4\/ferritin downregulation. In vivo, PACs-CFE ameliorated liver fibrosis, restored hepatic architecture, and improved serum alanine aminotransferase, aspartate aminotransferase, and bilirubin profiles. Moreover, PACs-CFE modulated the TGF-\u03b21\/Smad3 signaling pathway and beneficially reshaped the gut microbiota, enriching anti-inflammatory and hepatoprotective genera while reducing pathogenic taxa. Conclusions: Our findings show that PACs-CFE exerts multi-targeted anti-fibrotic effects through hepatic stellate cell inactivation, ferroptosis induction, TGF-\u03b21\/Smad3 suppression, and gut\u2013liver axis modulation. This study provides useful insight into the hepatoprotective potential of cili fruit and supports its development as standardized functional ingredients for liver health.<\/jats:p>","DOI":"10.3390\/nu17213463","type":"journal-article","created":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T14:00:33Z","timestamp":1762178433000},"page":"3463","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["A Proanthocyanidins-Rich Cili (Rosa roxburghii) Fruit Extract Protects CCl4-Induced Mouse Hepatic Fibrosis via Modulation of Ferroptosis and Gut Microbiota"],"prefix":"10.3390","volume":"17","author":[{"given":"Yang","family":"Liu","sequence":"first","affiliation":[{"name":"School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingzhong","family":"Zheng","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Zheng","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Zhou","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7565-6889","authenticated-orcid":false,"given":"Hang","family":"Ma","sequence":"additional","affiliation":[{"name":"Bioactive Botanical Research Laboratory, Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, The University of Rhode Island, Kingston, RI 02881, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4900-7671","authenticated-orcid":false,"given":"Xue","family":"Zhou","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fahuan","family":"Ge","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Yin, C., Zhang, Y., Zhang, L., Tian, Y., Zhong, X., Fang, X., Yang, Y., and Tao, A. 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