Anthocyanins improve liver fibrosis in mice by regulating the autophagic flux level of hepatic stellate cells by mmu_circ_0000623

• Published in: Food science & nutrition 2023-06, Vol.11 (6), p.3002-3018
• Main Authors: Du, Jinhui, Liu, Likun, Fan, Haiqing, Yu, Yue, Luo, Yilin, Gu, Fang, Yu, Hui, Liao, Xin
• Format: Article
• Language: English
• Subjects: Anthocyanins; autophagy; Blueberries; Cell growth; circRNA; Cirrhosis; Enzyme-linked immunosorbent assay; Epigenetics; Fibrosis; Fluctuations; hepatic stellate cells; Hepatocytes; Laboratory animals; Leukocyte migration; Liver; Liver cancer; Liver cirrhosis; Liver diseases; liver fibrosis; Macrophages; Molecular modelling; Original; Polymerase chain reaction; Proteins; Stellate cells; Western blotting
• ISSN: 2048-7177; 2048-7177
• DOI: 10.1002/fsn3.3281

Liver fibrosis is a key step in the progression of various chronic liver diseases to liver cirrhosis and even liver cancer, it is also an important link affecting prognosis. Therefore, this study aimed to investigate the therapeutic effect of anthocyanins on liver fibrosis and the molecular mechanism of mmu_circ_0000623 in anthocyanin therapy. In this study, CCL4 was used to build a mouse liver fibrosis model, and the treatment groups were treated with 100 and 200 mg/kg of anthocyanins daily by gavage. Liver fibrosis indicators, macrophage polarization markers, and liver injury markers were further detected by real‐time quantitative PCR (qRT‐PCR), western blotting (WB), and enzyme‐linked immunosorbent assay. Morphological verification of liver injury in different treatment groups was performed by histopathological method. A mouse hepatic stellate cell (HSC) model and a mouse liver fibrosis model were constructed to verify the expression of circ_0000623, miR‐351‐5p, and TFEB. Transfected with mRFP‐GFP‐LC3 to detect the autophagic flux of HSCs. We found that 100 mg/kg or 200 mg/kg of anthocyanins could significantly reduce the degree of liver fibrosis in mice. In addition, anthocyanins can inhibit the proliferation, activation, and migration ability of HSCs. circ_0000623 was lowly expressed in mice with liver fibrosis, and anthocyanin treatment could promote its increased expression. Further testing found that anthocyanins could reverse the blocked autophagic flux induced by PDGF or CCL4. This effect is achieved by regulating the expression of TFEB by competitive adsorption of miR‐351‐5p. Anthocyanins could treat liver fibrosis by modulating circ_0000623/miR‐351‐5p/TFEB‐mediated changes in HSC autophagic flux. This study demonstrated for the first time that anthocyanins can participate in the process of liver fibrosis by regulating the autophagy level of hepatic stellate cells. For the first time, we confirmed the significance of mmu_circ_0000623 in the treatment of liver fibrosis with anthocyanins. Anthocyanins could treat liver fibrosis by modulating circ_0000623/miR‐351‐5p/TFEB‐mediated changes in HSC autophagic flux.