An in silico investigation on the interactions of curcumin and epigallocatechin-3-gallate with NLRP3 Inflammasome complex

Abstract

Interleukin-1β (IL-1β) and IL-18 are the underlying factors of the inflammatory response and are necessary for the host's reaction and pathogen resistance. These cytokines also promote damage during chronic inflammation along with acute tissue injury. However, little is known about how these proteins are made and secreted from cells. Inflammasomes are multi-protein complexes which are required for the canonical synthesis of IL-1β. The NLRP3 inflammasome complex is one of the most studied inflammasome complexes. Its activation is dependent on two signals, i.e. one "primes" the cells by inducing the production of NLRP3 and pro-IL-1β, while the other causes the complex to assemble and activate. Lysosomal rupture, reactive oxygen species, and cytosolic ion perturbation function as the second signal. Despite extensive research, the exact role and regulation of the NLRP3 inflammasome are still unknown. In the current study, we investigated the inhibitory effect of plant-derived compounds such as curcumin and epigallocatechin-3-gallate (EGCG) on NLRP3-mediated IL-1β and IL-18 production using in silicoapproach. Our data suggest that the therapeutic effect of curcumin and EGCG may be due to the inhibition of inflammasome activation. The molecular and protein-protein interaction data indicated that the therapeutic effects of these two polyphenols are mediated by preventing the development of the NLRP3 complex.