A Protective Role of Glibenclamide in Inflammation-Associated Injury

Figure 1

Anti-inflammatory mechanisms of glibenclamide. Glibenclamide blocks KATP channel to prevent K⁺ efflux and changes the membrane potential, which inhibits P2X7 receptor-mediated Ca²⁺ influx, resulting in reducing inflammatory cytokines. Glibenclamide blocks the Sur1-Trpm4 channel to decrease the BBB permeability, which reduces extravasated protein-induced production of TNF-α. Glibenclamide inhibition of Sur1-Trpm4 channel increases ROCE-mediated Ca²⁺ influx, which activates CaMKII and then inhibits CN/NFAT/Nos2 signaling. Glibenclamide can inhibit NLRP3 inflammasome-mediated production of IL-1β and reduce IL-13/4, which blocks the migration of eosinophils. The inhibitory effect is indicated by red lines with bar ends; the excitatory effect is indicated by green lines with arrow ends. ROCE: receptor-operated Ca²⁺ entry channel; CaMKII: Ca²⁺/calmodulin protein kinase II; CN: calcineurin; NFAT: nuclear of activated T cells; Nos2: inducible nitric oxide synthase gene; AP-1: activator protein-1; ERKs: extracellular signal-regulated kinases; JNKs: Jun N-terminal kinases; BBB: blood-brain barrier; p-STAT6: phosphorylated signal transducer and activator of transcription 6; VCAM-1: vascular cell adhesion molecular 1.