Nutrients, Vol. 17, Pages 3463: A Proanthocyanidins-Rich Cili (Rosa roxburghii) Fruit Extract Protects CCl4-Induced Mouse Hepatic Fibrosis via Modulation of Ferroptosis and Gut Microbiota

Nutrients, Vol. 17, Pages 3463: A Proanthocyanidins-Rich Cili (Rosa roxburghii) Fruit Extract Protects CCl4-Induced Mouse Hepatic Fibrosis via Modulation of Ferroptosis and Gut Microbiota

Nutrients doi: 10.3390/nu17213463

Authors:
Yang Liu
Jingzhong Zheng
Xin Zheng
Dan Zhou
Hang Ma
Xue Zhou
Fahuan Ge

Background: Cili (Rosa roxburghii Tratt) is a unique fruit native to China’s Yunnan–Guizhou Plateau, rich in vitamin C, polyphenols, and triterpene, with broad health-promoting effects. Although cili’s 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 α-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-β1/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-β1/Smad3 suppression, and gut–liver 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.

​Background: Cili (Rosa roxburghii Tratt) is a unique fruit native to China’s Yunnan–Guizhou Plateau, rich in vitamin C, polyphenols, and triterpene, with broad health-promoting effects. Although cili’s 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 α-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-β1/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-β1/Smad3 suppression, and gut–liver 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. Read More

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