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].
Ac-YVAD-cmk 细胞实验
Cell Line
Concentration
Treated Time
Description
References
PBMCs-derived primary monocytes
10 µM
1 hour
Inhibited CASPASE-1 enzymatic activity, blocked IL-1β secretion and LDH release, but did not affect FADD secretion
Cell Death Dis. 2019 Feb 25;10(3):190.
THP-1 monocytes
10 µM
1 hour
Inhibited CASPASE-1 enzymatic activity, blocked IL-1β secretion and cell death, but did not affect FADD secretion
Cell Death Dis. 2019 Feb 25;10(3):190.
mouse macrophages
100 μM
1 hour
Inhibited caspase 1 activity, protecting macrophages from Flagellin+ Legionella pneumophila-induced death
J Exp Med. 2006 Apr 17;203(4):1093-104.
Human pulmonary microvascular endothelial cells (HPMEC)
50 μM/mL
30 min
To investigate the effect of Ac-YVAD-cmk on bleomycin-induced endothelial-to-mesenchymal transition (EndoMT) in HPMEC. Results showed that YVAD significantly reduced the expression of caspase-1 p20 and NLRP3, and decreased the expression of EndoMT markers α-SMA and vimentin, while preserving VE-cadherin expression.
Int J Mol Sci. 2023 Oct 31;24(21):15813.
bone marrow-derived macrophages (BMDMs)
25μM
18 h
inhibited caspase-1 activity, significantly reduced IL-1β production
Cell Rep. 2019 Feb 5;26(6):1614-1626.e5.
C2C12 cells
25 μM
1 or 4 h
To investigate the effect of Ac-YVAD-CMK on PD-induced inflammatory response in C2C12 cells. Results showed that Ac-YVAD-CMK significantly inhibited PD-induced upregulation of Il-6 and Il-1β mRNA expression.
Cells. 2022 Jan 1;11(1):134.
HepG2 cells
100 μM
1 hour
Inhibited caspase-1 activity, significantly reducing LPS and ATP or LPS and nigericin-induced caspase-1 activation
Int J Mol Sci. 2020 Apr 30;21(9):3196.
Ac-YVAD-cmk 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
C57BL/6 mice
Bleomycin-induced pulmonary fibrosis model
Intraperitoneal injection
8 mg/kg
Single dose, observed for 7, 14, and 21 days
To investigate the effect of Ac-YVAD-cmk on bleomycin-induced pulmonary fibrosis. Results showed that YVAD significantly alleviated lung inflammation and fibrosis, reduced the expression of NLRP3 inflammasome and caspase-1 p20, and decreased the expression of EndoMT markers α-SMA and vimentin, while preserving VE-cadherin expression.
Int J Mol Sci. 2023 Oct 31;24(21):15813.
BALB/c mice
Intramuscular injection model
Intramuscular injection
1 μg/g
1 hour before immunization and on day 15
To evaluate the effect of Ac-YVAD-CMK on the adjuvant activity of PD. Results showed that Ac-YVAD-CMK significantly inhibited PD-induced local inflammatory response and immune cell recruitment, and impaired the adjuvant activity of PD on OVA-specific immune responses.
Cells. 2022 Jan 1;11(1):134.
Mice
Subarachnoid hemorrhage model
Intraperitoneal injection
6mg/kg or 10mg/kg
Single dose, observed for 24 hours
To investigate the effect of Ac-YVAD-CMK on neurogenic pulmonary edema after subarachnoid hemorrhage. Results showed that 10mg/kg of Ac-YVAD-CMK significantly inhibited pulmonary edema and endothelial cell apoptosis, reducing mortality.
Stroke. 2009 Dec;40(12):3872-5
Mice
LPS-induced ALI/ARDS model
Intraperitoneal injection
6.5 mg/kg
Single dose, evaluated after 24 hours
To evaluate the effect of Ac-YVAD-cmk on alveolar macrophage pyroptosis and NETs levels in LPS-induced ALI/ARDS model, results showed that Ac-YVAD-cmk significantly reduced alveolar macrophage pyroptosis and NETs levels, and alleviated lung inflammation and injury.
J Inflamm Res. 2021 Sep 21;14:4839-4858
Mice
IL-10 knockout mice
Intraperitoneal injection
1.25 mg/kg
2 weeks
To investigate the effect of inhibiting inflammasome activation on chronic colitis. Results showed that Ac-YVAD-cmk treatment significantly ameliorated spontaneous colitis in IL-10 KO mice.
Mucosal Immunol. 2014 Sep;7(5):1139-50
Mouse
URI(Δ/Δ)Int mouse model
Intraperitoneal injection
8 mg/kg
Daily until sacrifice
Inhibit pyroptosis, restore R-spondin levels, and partially restore intestinal architecture
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