A Protective Role of Glibenclamide in Inflammation-Associated Injury

Abstract

Glibenclamide is the most widely used sulfonylurea drug for the treatment of type 2 diabetes mellitus (DM). Recent studies have suggested that glibenclamide reduced adverse neuroinflammation and improved behavioral outcomes following central nervous system (CNS) injury. We reviewed glibenclamide's anti-inflammatory effects: abundant evidences have shown that glibenclamide exerted an anti-inflammatory effect in respiratory, digestive, urological, cardiological, and CNS diseases, as well as in ischemia-reperfusion injury. Glibenclamide might block KATP channel, Sur1-Trpm4 channel, and NOD-like receptor pyrin domain containing 3 (NLRP3) inflammasome activation, decrease the production of proinflammatory mediators (TNF-α, IL-1β, and reactive oxygen species), and suppress the accumulation of inflammatory cells. Glibenclamide's anti-inflammation warrants further investigation.

Glibenclamide ameliorates the disrupted blood–brain barrier in experimental intracerebral hemorrhage by inhibiting the activation of NLRP3 inflammasome

“…Genetic depletion of NLRP3 significantly attenuates inflammation and injury after ICH, indicating that drugs that can manipulate the activation of NLRP3 inflammasome are promising therapeutic strategies for patients with ICH (Yuan et al, ). Several in vivo and in vitro experiments have confirmed that glibenclamide can effectively inhibit the activation of NLRP3 inflammasome Zhang et al, ). A plausible mechanism underlying inhibition of the NLRP3 inflammasome is that glibenclamide prevents cellular efflux of K + by inhibiting the regulatory subunit of ATP‐sensitive potassium channels (K ATP ) on the cell membrane.…”

“…Growing evidence suggests that glibenclamide inhibits neuroinflammation and improves behavioral outcomes following CNS injury (Zhang et al, ). Our present results demonstrate that glibenclamide attenuated cerebral edema, neuroinflammation, disruption of the BBB, and neurological deficit after ICH.…”

Effects of glucose-lowering agents on surrogate endpoints and hard clinical renal outcomes in patients with type 2 diabetes

“…In contrast to the huge amount of experimental animal data supporting the renal-protective effects of metformin [37], no such data are available in the literature for sulphonylureas [38,39].…”

Glyburide inhibits the bone resorption induced by traumatic occlusion in rats

“…Glyburide is an K ATP channel inhibitor that has been reported to suppress activation of NLRP3 inflammasomes and is frequently used as an NLRP3 inflammasome inhibitor . Glyburide suppresses NLRP3‐dependent caspase‐1 activation and IL‐1β expression in mouse bone marrow‐derived macrophages after stimulation with LPS and ATP .…”