Network pharmacology analysis and experimental validation of EGCG's therapeutic effects against acute lung injury in sepsis.

BACKGROUND

Acute lung injury (ALI), a severe pulmonary condition associated with sepsis, involves deterioration of alveolar and capillary endothelial cells during initial stages. Current therapeutic interventions remain insufficient.

OBJECTIVE

This study investigates the therapeutic epigallocatechin gallate (EGCG) on sepsis-induced ALI and its underlying molecular mechanisms.

METHODS

The effects of EGCG on M1 macrophage polarization and its glycolytic activity in sepsis models were evaluated through both in vitro and in vivo experiments. The targets of EGCG were identified using network pharmacology and molecular docking techniques, which were subsequently validated through experimental studies. The CCK-8 assay was employed to determine the optimal concentration of EGCG for maintaining the highest viability of LPS-treated RAW264.7 macrophages and bone marrow-derived macrophages (BMDMs). The sepsis models utilized included LPS-treated cell models and murine models established via cecal ligation and puncture (CLP). These models were evaluated through various biological methodologies, including qPCR, ELISA, and Western blot analysis across multiple dimensions.

RESULTS

EGCG effectively reduced the expression of HK2, PKM2, and iNOS, mitigating lung damage in CLP mice. Network pharmacology analysis identified the epidermal growth factor receptor (EGFR) as a primary target, associated with the HIF-1α pathway. Mechanistically, EGCG reduced p-EGFR/EGFR, suppressing the expression of HIF-1α, HK2, PKM2, and iNOS.

CONCLUSIONS

EGCG reduces ALI caused by sepsis by inhibiting macrophage glycolysis through the EGFR/HIF-1α signaling pathway.