Inhibition of NLRP3-inflammasome mediated IL-1β release by phenylpropanoic acid derivatives: in-silico and in-vitro approach

NLRP3 inflammasome activation and subsequent release of IL-1β are being explored as a causal pathology for inflammatory and autoimmune disorders. Modulation of this pathway by the compounds from natural sources may provide a better targeted approach with improved therapeutic outcome. The study was carried out to test the ability of phenylpropanoic acid derivatives to inhibit the NLRP3 inflammasome pathway and IL-1β release. The main purpose of the study was to test the active derivatives with respect to the possible molecular interactions in-silico, effect on mRNA expression of molecular markers and, effect on released cytokine. Autodock along with SwissADME was used to carry out the in-silico studies including the prediction studies as well as molecular docking studies. The effect of test compounds on mRNA expression of important proteins was evaluated against U87MG cells using RT-qPCR. The changes in released cytokine levels was evaluated using ELISA. The tested phenylpropanoic acid derivatives had a comparable molecular docking profile to that of selected standards. The prediction studies indicated that these compounds have suitable properties to be a drug candidate. mRNA expression studies showed that the derivatives can downregulate the proteins responsible for inflammasome activation and same was reflected in ELISA when the concentration of released cytokine was evaluated. Based on the above results, phenylpropanoic acid derivatives have potential to be developed as specific NLRP3-inflammasome inhibitors.