Epigallocatechin Gallate Attenuates High-Fat Emulsion–Induced Pyroptosis in HepG2 Cells by Inhibiting the NLRP3–Caspase-1–GSDMD Pathway

Objective To investigate the role of the pyroptosis pathway in high-fat emulsion–induced injury of HepG2 cells and to evaluate the protective effect of epigallocatechin gallate (EGCG). Methods An in vitro NAFLD model was established by exposing HepG2 cells to a high-fat emulsion, followed by treatment with varying concentrations of EGCG. Anti-NAFLD effects were assessed by evaluating cell viability, lipid accumulation, lipoprotein levels, inflammatory cytokines, and LDH release. The underlying mechanism was explored using flow cytometry, transmission electron microscopy, scanning electron microscopy, RT-PCR, Western blotting, and immunofluorescence. Results EGCG treatment markedly improved cell viability, reduced lipid accumulation, normalized lipoprotein profiles, and decreased inflammatory cytokine levels and LDH release. EGCG also ameliorated morphological and biochemical features of high-fat emulsion–induced pyroptosis, lowering the proportion of pyroptotic cells. Furthermore, EGCG significantly downregulated the mRNA and protein expression of NLRP3, Caspase-1, and GSDMD, reduced fluorescence intensity, and diminished GSDMD localization to the plasma membrane. Conclusions High-fat emulsion induces HepG2 cell pyroptosis via the NLRP3–Caspase-1–GSDMD pathway. EGCG attenuates lipid deposition and pyroptosis in this model, potentially through inhibition of the classical NLRP3–Caspase-1–GSDMD signaling axis.