Bellidifolin alleviates doxorubicin-induced hepatotoxicity: a study integrating network pharmacology, molecular docking, and experimental validation.

This study aimed to investigate the protective role of bellidifolin (BEL) in doxorubicin (DOX)-induced liver injury and explore its underlying mechanisms. Through network pharmacology, potential targets and pathways of BEL against DOX-induced liver injury were identified. Molecular docking and molecular dynamics simulation were employed to further verify the binding activity of BEL to the core targets. Mice were randomly divided into three groups: control (CON), DOX (DOX) and BEL treated group (BEL). Liver pathological changes were evaluated through HE and Masson staining, serum ALT and AST were detected using a biochemical analyzer, and predicted pathway related proteins were assessed through immunohistochemistry staining and western blot analysis.

Results

BEL alleviated DOX-induced liver injury in mice, as evidenced by attenuated hepatic pathological changes and fibrosis, decreased serum levels of ALT and AST, and inhibition of hepatocyte pyroptosis. The network pharmacology analysis revealed that the key targets of BEL in treating DOX-induced liver injury include Caspase-1, NLRP3, IL-18 and IL-1β, etc. The GO and KEGG analyses revealed that BEL's mechanism of action involves the NLRP3 pathways. Molecular docking and molecular dynamics simulation indicated that BEL exhibits strong binding affinity for both Galectin-3 (Gal-3) and NLRP3. Western blot and immunohistochemistry staining further confirmed that BEL inhibited the expression of proteins in the Gal-3/NLRP3 signaling pathway.

Conclusion

BEL may alleviate DOX-induced liver injury by inhibiting Gal-3/NLRP3-mediated pyroptosis.