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

• Published in: Biomedicine & pharmacotherapy 2022-12, Vol.156, p.113890-113890, Article 113890
• Main Authors: Jena, Atala B., Dash, Umesh C., Duttaroy, Asim K.
• Format: Article
• Language: English
• Subjects: Antioxidant; Caspase-1; Curcumin; EGCG; Inflammasome; Polyphenols
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2022.113890

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. The NLRP3 inflammasome involves in the secretion of pro-inflammatory cytokines IL-1β/IL-18 in response to microbial infection and cellular damage. Curcumin and epigallocatechin-3-gallate (EGCG) suppress the activation of the NLRP3 inflammasome; however, the exact mechanisms are not yet well known. In the current study, we investigated the interaction of curcumin and EGCG, the plant-derived compounds, with NLRP3 complex using in silico approach. The molecular docking and protein-protein interaction were used to investigate the apparent binding processes and affinities between components of the NLRP3 complex with curcumin and EGCG. Our data showed that NLRP3 had a higher binding affinity for curcumin and EGCG than other complex proteins, with − 8.2 Kcal/mol and − 9.6 Kcal/mol, respectively. Similarly, ASC had a lower binding affinity for curcumin and EGCG, with − 5.0 Kcal/mol and − 7.4 Kcal/mol, respectively. The higher binding affinity of both compounds for the key NLRP3 protein in their complexes as compared to that of MCC950 (a selective inhibitor of NLRP3 complex) suggests that curcumin and EGCG may impact the complex's function. Protein-protein interaction studies also corroborated the efficacy of these two polyphenols in hindering the formation of NLRP3 complex. 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. Proposed mechanisms to prevent the development of the NLRP3 complex by antioxidant curcumin and catechin. [Display omitted] •NLRP3 inflammasome promotes caspase-1 activation, and the release of cytokines IL-1 and IL-18 leads to cellular injury.•The binding energies of curcumin and inhibitor MCC950 are almost identical.•Protein-protein interactions indicate that these two polyphenols effectively prevent the formation of the NLRP3 complex.•Curcumin and EGCG, plant-derived compounds, inhibit the NLRP3-mediated IL-1β and IL-18 production.