Glibenclamide Prevents Inflammation by Targeting NLRP3 Inflammasome Activation in vitro

Abstract

The NLRP3 inflammasome plays a significant role in the development of neurodegeneration, physiological aging and metabolic inflammation, which actualizes the search for effective NLRP3 inflammasome inhibitors and assessing their effects. This study was aimed to assess the effect of pharmacological modulation of NLRP3 activity by an indirect NLRP3 inflammasome inhibitor, glibenclamide, on the in vitro expression of metaflammasome components in brain cells derived from middle-aged mice. It was found that glibenclamide reduces the expression of pro-inflammatory markers NLRP3 and IL18 in cell culture, which in turn prevents the phosphorylation of metaflammasome complex protein kinases, PKR and IKKβ. At the same time, there were no changes in the expression of pathologically phosphorylated IRS, as well as in the number of senescent cells in cultures after glibenclamide exposure.