Mechanism of DCA in sepsis and liver injury based on network pharmacology and molecular docking

AimTo evaluate the potential of(dichloroacetate, DCA)in sepsis and liver injury using network pharmacology and molecular docking and to validate it through animal models.MethodsWe predicted DCA's potential drug targets through public databases. Further, it used DisGeNET database to collect sepsis and liver damage-related genes, and intersected them with DCA targets to construct a protein-protein interaction network between drug targets and disease genes, followed by molecular docking to assess key therapeutic targets. A mouse model of sepsis with liver injury was established. After DCA intervention, liver tissue was collected for mass spectrometry and protein quantification six hours post-intervention, followed by intergroup comparison of DCA-targeted sites.ResultsMolecular docking indicated that DCA had a strong binding affinity with targets such as PPARA, F2, HSP90AA1, PDK1, ARG1, NOS3 and CAT. In the mouse model, while only CAT and PDK1 exhibited statistically significant differences between the groups. DCA's interactive targets in sepsis and liver injury were mainly enriched in metabolism and immunityrelated biological processes. KEGG pathway enrichment analysis showed that DCA's interactive disease targets were primarily enriched in the interleukin-17 (IL-17)signaling pathway and the Toll-like receptor (TLR)signaling pathway.ConclusionDCA demonstrates significant pharmacological activity in sepsis and liver injury, identifying catalase(CAT)and pyruvate dehydrogenase kinase 1(PDK1)as potential key targets.