Epigallocatechin gallate (EGCG) attenuates staphylococcal alpha-hemolysin (Hla)-induced NLRP3 inflammasome activation via ROS-MAPK pathways and EGCG-Hla interactions

Alpha-hemolysin (Hla), the virulence factor secreted by Staphylococcus aureus (S. aureus), plays a critical role in Infection and inflammation, which is a severe health burden worldwide. Therefore, it is necessary to develop a drug against Hla. Epigallocatechin gallate (EGCG), a polyphenol extracted from green tea, has excellent anti-inflammatory activity. In this study, we investigated the inhibitory effect of EGCG on Hla-induced NLRP3 inflammasome activation in vitro and in vivo and elucidated the potential molecular mechanism. We found that EGCG attenuated the hemolysis of Hla by inhibiting its secretion. Besides, EGCG significantly decreased overproduction of ROS and activation of MAPK signaling pathway induced by Hla, thereby markedly attenuating the expression of NLRP3 inflammasome-related proteins in THP-1 cells. Notably, EGCG could spontaneously bind to Hla with affinity constant of 1.71 × 10^-4 M, thus blocking the formation of the Hla heptamer. Moreover, Hla-induced expression of NLRP3, ASC and Caspase-1 protein and generation of IL-1β and IL-18 in the damaged liver tissue of mice were also significantly suppressed by EGCG in a dose-dependent manner. Collectively, EGCG could be a promising candidate for alleviating Hla-induced the activation of NLRP3 inflammasome, depending on ROS mediated MAPK signaling pathway, and inhibition of Hla secretion and heptamer formation. These findings will enlighten the applications of EGCG to reduce the S. aureus Infection by targeting Hla in food and related pharmaceutical fields.