Caspase-1 is a key enzyme of the NLRP3 inflammasome, which is a critical pro-inflammatory mediator that modulates host responses to various stress conditions[3]. Ac-YVAD-CMK inhibited activation of M1 microglial and enhanced M2 microglial activation after ICH (Intracerebral hemorrhage)[4]. In mice, Caspase-1 activation was inhibited significantly in a dose-dependent manner by pretreatment with AC-YVAD-CMK (1.25, 6.25, and 12.5 μmol/kg). Furthermore, AC-YVAD-CMK (12.5 μmol/kg) pretreatment significantly reduced the cold-restraint stress induced multiple haemorrhagic gastric erosions and ulcers, as well as the elevated levels of IL-1β, IL-18 and CD68 mRNA expression. Treatment of mice with AC-YVAD-CMK (12.5 μmol/kg) 30 min before cold-stress injury decreased the mortality rate compared with mice that received vehicle. Moreover, AC-YVAD-CMK (12.5 μmol/kg) alleviated the overexpression of phospho (P)-P38 protein and P-IκB induced by cold-restraint stress. In addition, ethanol induced multiple haemorrhagic erosions and ulcers were also alleviated significantly by pretreatment with AC-YVAD-CMK (12.5 μmol/kg)[3]. AC-YVAD-CMK treatment improved rotarod performance time after 72 hrs as compared with ICH group[4].
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