Epigallocatechin-3-gallate alleviates trans, trans -2,4-decadienal-induced endothelial pyroptosis and dysfunction by inhibiting NLRP3 inflammasome activation

Trans, trans -2,4-decadienal (tt-DDE) is a highly reactive unsaturated aldehyde that widely present in foods. This study aimed to investigate the toxic effects of tt-DDE exposure on human umbilical vein endothelial cells (HUVECs) and the possible protective effects of green tea catechins. tt-DDE exposure induced pyroptosis and NLRP3 inflammasome activation in endothelial cells, as evidenced by increased LDH release and PI-positive cells, and elevated protein expressions of NLRP3, cleaved caspase-1, and GSDMD-N. NLRP3 inhibitor (MCC950) efficiently suppressed the tt-DDE-induced NLRP3 inflammasome activation and pyroptosis. Additionally, epigallocatechin-3-gallate (EGCG) showed the strongest activity among the four green tea catechins, which significantly alleviated tt-DDE-induced cytotoxicity. Moreover, EGCG effectively attenuated tt-DDE-induced endothelial cell pyroptosis and dysfunction by inhibiting NLRP3 inflammasome. Results of cultured mesenteric arteries further confirmed that EGCG prevented tt-DDE-induced endothelial dysfunction and pyroptosis. These results provide novel insights into tt-DDE-induced endothelial injury, and demonstrate the protective role of EGCG against tt-DDE-associated endothelial toxicity.