Abstract
Lipopolysaccharide (LPS)-induced hepatic inflammation plays a crucial role in the pathogenesis of various liver diseases. Quercetin, a natural flavonoid, has demonstrated anti-inflammatory effects in different models of inflammation. However, its role in LPS-induced hepatic inflammation remains unclear. This study aimed to investigate the protective effects of quercetin against LPS-induced hepatic inflammation and explore the underlying mechanisms.
Methods
Hepatic inflammation was induced in mice by intraperitoneal injection of LPS. Quercetin was administered before LPS injection. Liver injury was assessed by measuring serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels. Histopathological examination was performed to evaluate liver morphology. The expression of inflammatory cytokines and the activation of autophagy and necroptosis were determined by Western blotting and immunofluorescence staining.
Results
Quercetin pretreatment significantly attenuated LPS-induced liver injury, as evidenced by reduced serum ALT and AST levels and improved liver morphology. Quercetin inhibited the expression of pro-inflammatory cytokines, including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6). Moreover, quercetin upregulated the expression of autophagy-related proteins, such as LC3B and Beclin-1, and increased the formation of autophagosomes. In contrast, quercetin suppressed the activation of necroptosis, as indicated by decreased expression of RIPK1, RIPK3, and MLKL. Further studies revealed that quercetin inhibited the interaction between RIPK1 and RIPK3, thereby blocking the formation of the necrosome.
Conclusions
Quercetin alleviates LPS-induced hepatic inflammation by regulating autophagy and necroptosis. Its anti-inflammatory effects are mediated by the inhibition of pro-inflammatory cytokine expression, the upregulation of autophagy, and the suppression of necroptosis. These findings suggest that quercetin may be a promising therapeutic agent for the treatment of LPS-induced hepatic inflammation and related liver diseases.
Keywords: Quercetin; LPS; hepatic inflammation; autophagy; necroptosis
Conflict of interest
The authors declare no conflict of interest.
Acknowledgments
This study was supported by the National Natural Science Foundation of China (grant number 81970499).
Author contributions
- Conceptualization: J.X., Y.W.
- Data curation: J.X., Q.L.
- Formal analysis: J.X., Y.W.
- Funding acquisition: Y.W.
- Investigation: J.X., Q.L.
- Methodology: J.X., Q.L.
- Project administration: Y.W.
- Resources: Y.W.
- Software: J.X., Q.L.
- Supervision: Y.W.
- Validation: J.X., Q.L.
- Visualization: J.X., Y.W.
- Writing – original draft: J.X.
- Writing – review & editing: J.X., Y.W.
Kind regards
Dr. R. Naples