Anti-liver fibrosis effects of the total flavonoids of litchi semen on CCl4-induced liver fibrosis in rats associated with the upregulation of retinol metabolism

• Published in: Pharmaceutical biology Vol. 60; no. 1; pp. 1264 - 1277
• Main Authors: Yan, Jiongyi, Feng, Yinyi, Fang, Xuewan, Cui, Xiaojuan, Xia, Xing, Li, Fang, Luo, Weisheng, Liang, Jianqin, Feng, Jianfang, Yu, Kai
• Format: Journal Article
• Language: English
• Published: Abingdon Taylor & Francis 01-12-2022; Taylor & Francis Ltd; Taylor & Francis Group
• Subjects: 9-Cis-retinoic acid; Aldehyde dehydrogenase; Carbon tetrachloride; Fibrosis; Flavonoids; iTRAQ; Liver; liver disease; Metabolism; mRNA; Proteins; Proteomics; Retinoic acid; RXRα; traditional Chinese medicine; Up-regulation; Vitamin A
• ISSN: 1388-0209; 1744-5116
• DOI: 10.1080/13880209.2022.2086584

The litchi semen are traditional medications for treating liver fibrosis (LF) in China. The mechanism remains unclear.
This study investigates the anti-liver fibrotic mechanism of the total flavonoids of litchi semen (TFL).
Sprague-Dawley rats with carbon tetrachloride-induced LF were treated with TFL (50 and 100 mg/kg) for 4 weeks. The anti-liver fibrotic effects of TFL were evaluated and the underlying mechanisms were investigated via histopathological analysis, proteomic analysis and molecular biology technology.
Significant anti-LF effects were observed in the high-TFL-dose group (TFL-H, p < 0.05). Five hundred and eighty-five and 95 differentially expressed proteins (DEPs) were identified in the LF rat model (M group) and TFL-H group, respectively. The DEPs were significantly enriched in the retinol metabolism pathway (p < 0.0001). The content of 9-cis-retinoic acid (0.93 ± 0.13 vs. 0.66 ± 0.10, p < 0.05, vs. the M group) increased significantly in the TFL-H group. The upregulation of RXRα (0.50 ± 0.05 vs. 0.27 ± 0.13 protein, p < 0.05), ALDH2 (1.24 ± 0.09 vs. 1.04 ± 0.08 protein, p < 0.05), MMP3 (0.89 ± 0.02 vs. 0.61 ± 0.12 protein, p < 0.05), Aldh1a7 (0.20 ± 0.03 vs. 0.03 ± 0.00 mRNA, p < 0.05) and Aox3 (0.72 ± 0.14 vs. 0.05 ± 0.01 mRNA, p < 0.05) after TFL treatment was verified.
TFL exhibited good anti-liver fibrotic effects, which may be related to the upregulation of the retinol metabolism pathway. TFL may be promising anti-LF agents with potential clinical application prospects.