GYY4137 is a slow-release H2S donor with vasodilatory and antihypertensive activities. GYY4137 also exhibits anti-inflammatory and anticancer activities[1][2][3].In the concentration range of 400-800 μM, GYY4137 exhibited concentration-dependent killing of seven different human cancer cell lines (HeLa, HCT-116, Hep G2, HL-60, MCF-7, MV4-11, and U2OS) without affecting the survival of normal human lung fibroblasts (IMR90, WI-38)[2].In the concentration range of 0.1-0.5 mM, GYY4137 reduced LPS-induced production of nitrite (NO2), PGE2, TNF-α, and IL-6 in human synoviocytes (HFLS) and articular chondrocytes (HAC), decreased the levels and catalytic activities of inducible nitric oxide synthase (iNOS) and cyclo-oxygenase-2 (COX-2), and reduced LPS induced NF-κB activation[3].
GYY4137 细胞实验
Cell Line
Concentration
Treated Time
Description
References
HCT116 cells
1-3 mM
48 hours
Activated the CyR61 promoter in a concentration-dependent fashion
Redox Biol. 2022 Oct;56:102466
Jurkat T cells
0.5 mM
Validated that the protective effect of H2S on reducing H2O2-induced Golgi stress depends on Prdx4 by mutating the C51A site of Prdx4
Sci Adv. 2024 Nov 15;10(46):eadp1152
Pmel CD8+ T cells
0.5 mM
7 days
Enhanced effector function, increased secretion of TNFα and IFN-γ, as well as granzyme B and CD107 expression
Sci Adv. 2024 Nov 15;10(46):eadp1152
HT-29 cells
50 μM
48 hours
To investigate the protective effect of GYY4137 on LPS-induced damage in HT-29 cells. Results showed that GYY4137 reduced COX-2 expression by increasing the sulfhydration level of HuR.
J Adv Res. 2023 Feb;44:201-212
Caco-2 cells
50 μM
48 hours
To investigate the protective effect of GYY4137 on LPS-induced damage in Caco-2 cells. Results showed that GYY4137 reduced COX-2 expression by increasing the sulfhydration level of HuR.
J Adv Res. 2023 Feb;44:201-212
RFL-6 cells
10-100 μM
45 min
To investigate the modulation of intracellular sulfide levels by GYY4137 and its effect on SNAP-induced sGC activation. Pre-incubation with GYY4137 increased intracellular sulfide levels and inhibited SNAP-induced cGMP increases.
Redox Biol. 2014 Jan 11;2:234-44
HL-1 cells
100 μmol/L
48 hours
To simulate type 2 diabetes conditions, GYY4137 treatment reduced lipid droplet formation.
MSCs were treated with H2S-pretreated M2 macrophage conditioned medium, showing increased osteogenic differentiation as indicated by alkaline phosphatase (ALP) and alizarin red S staining.
Bioact Mater. 2023 Aug 12;31:192-205
RAW 264.7 macrophages
50 μM
24 hours
To test the role of H2S on M2 polarization of macrophages, it was found that GYY4137 treatment promoted M2 macrophage polarization under IL-4 induction conditions, increasing the proportion of CD115+F4/80+ cells.
Bioact Mater. 2023 Aug 12;31:192-205
GYY4137 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Nude mice
Subcutaneous implantation of MSCs with hydroxyapatite/tricalcium phosphate (HA/TCP) scaffold
Subcutaneous implantation
50 μg exosomes
Single implantation, lasting 8 weeks
To verify the ability of H2S-pretreated M2 macrophage exosomes to promote osteogenic differentiation of MSCs and new bone formation in vivo, the results showed that H2S pretreatment significantly enhanced new bone formation.
Bioact Mater. 2023 Aug 12;31:192-205
Mice
LPS-induced colitis model
Intraperitoneal injection
500 μg/10 g
Once daily for 7 days
To investigate the protective effect of GYY4137 on LPS-induced colitis. Results showed that GYY4137 significantly alleviated the symptoms of LPS-induced colitis, reduced COX-2 expression, and increased the sulfhydration level of HuR.
J Adv Res. 2023 Feb;44:201-212
Db/db mice
Type 2 diabetes model
Intraperitoneal injection
133 μM/kg/day
Once daily for 4 weeks
GYY4137 significantly reduced triglyceride levels in db/db mice and decreased lipid droplet accumulation in cardiac tissues.
H2S-pretreated T cells showed superior tumor control and prolonged survival
Sci Adv. 2024 Nov 15;10(46):eadp1152
GYY4137 动物研究
Animal study
Administered intraperitoneally at a dose of 100-300 mg/kg and administered once daily for 14 days, GYY4137 significantly reduced tumour volume in both animal models in a dose-dependent manner[2].In complete Forsythia adjuvant (CFA)-treated mice, GYY4137 (50 mg/kg, i.p.) increased knee swelling in the animals, whereas injection of GYY4137 6 hours after CFA produced an anti-inflammatory effect manifested by a decrease in synovial myeloperoxidase (MPO) and N-acetyl-β-D-glucosaminidase (NAG) activities, and a decrease in TNF-α, IL-1 β, IL-6 and IL-8 concentrations[3].GYY4137 significantly inhibited tumour growth in a subcutaneous HepG2 xenograft model by inhibiting STAT3 activation and the expression of its target genes[4].GYY4137 prevents nitrosative stress and α-synuclein nitration in a mouse model of MPTP-induced Parkinson's disease[5].
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