Quercetin alleviates liver fibrosis via regulating glycolysis of liver sinusoidal endothelial cells and neutrophil infiltration
DOI:
https://doi.org/10.17305/bb.2024.10530Keywords:
Quercetin, liver fibrosis, glycolysis, liver sinusoidal endothelial cell, neutrophil infiltrationAbstract
Liver fibrosis, a common characteristic in various chronic liver diseases, is largely influenced by glycolysis. Quercetin (QE), a natural flavonoid known to regulate glycolysis, was studied for its effects on liver fibrosis and its underlying mechanism. Results showed that QE effectively improved liver injury and fibrosis caused by carbon tetrachloride (CCl4). This was supported by evidence of improved pathological features and reduced levels of serum markers such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), γ-glutamyl transferase (GGT), total bile acid (TBA), total bilirubin (TBIL), direct bilirubin (DBIL), hyaluronic acid (HA), laminin (LN), and procollagen type III. QE also decreased lactate production and downregulated the expression of glycolysis-related enzymes – pyruvate kinase M2 (PKM2), phosphofructokinase platelet (PFKP), and hexokinase 2 (HK2) – at both the mRNA and protein levels. In liver sinusoidal endothelial cells (LSECs), QE reduced the expression and activity of these enzymes, resulting in reduced glucose consumption, ATP production, and lactate generation. Further analysis revealed that QE inhibited the production of chemokine (C-X-C motif) ligand 1 (CXCL1) and suppressed neutrophil recruitment. Overall, QE showed promising therapeutic potential for liver fibrosis by targeting LSEC glycolysis and reducing neutrophil infiltration.
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Data Availability Statement
The datasets generated and/or analyzed during the current study are available from the corresponding author (F.Y.) on a reasonable request.
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Copyright (c) 2024 Xiaoying Chen, Yifan Wang, Jie Wan, Xiaoyun Dou, Chuzhao Zhang, Meng Sun, Fang Ye
This work is licensed under a Creative Commons Attribution 4.0 International License.