Glibenclamide Prevents Inflammation by Targeting NLRP3 Inflammasome Activation in vitro

• Published in: Journal of evolutionary biochemistry and physiology Vol. 60; no. 3; pp. 1014 - 1026
• Main Authors: Khilazheva, E. D., Panina, Yu. A., Mosiagina, A. I., Belozor, O. S., Komleva, Yu. K.
• Format: Journal Article
• Language: English
• Published: Moscow Pleiades Publishing 01-05-2024; Springer Nature B.V
• Subjects: Animal Physiology; Biochemistry; Biomedical and Life Sciences; Cell culture; eIF-2 kinase; Evolutionary Biology; Experimental Papers; Glibenclamide; Inflammasomes; Inflammation; Life Sciences; Metabolic rate; Neurodegeneration; Phosphorylation; metaflammasome; senescence; old age; astrocytes; aging; NLRP3 inflammasome; glibenclamide; neurons; metainflammation
• ISSN: 0022-0930; 1608-3202
• DOI: 10.1134/S002209302403013X

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.