Hydroxysafflor Yellow A Inhibits Pyroptosis and Protecting HUVECs from OGD/R via NLRP3/Caspase-1/GSDMD Pathway.
10.1007/s11655-023-3716-y
- Author:
Fan GUO
1
;
Xiao HAN
1
;
Yue YOU
1
;
Shu-Juan XU
1
;
Ye-Hao ZHANG
1
;
Yuan-Yuan CHEN
1
;
Gao-Jie XIN
1
;
Zi-Xin LIU
1
;
Jun-Guo REN
1
;
Ce CAO
1
;
Ling-Mei LI
2
,
3
;
Jian-Hua FU
1
Author Information
1. Institute of Basic Medical Sciences of Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, 100091, China.
2. Institute of Basic Medical Sciences of Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, 100091, China. lilingmei0018@
3. com.
- Publication Type:Journal Article
- Keywords:
Chinese medicine;
NLRP3 inflammasome;
human umbilical vein endothelial cells;
hydroxysafflor yellow A;
myocardial reperfusion injury;
oxygen-glucose deprivation reperfusion;
pyroptosis
- MeSH:
NLR Family, Pyrin Domain-Containing 3 Protein/metabolism*;
Human Umbilical Vein Endothelial Cells/metabolism*;
Humans;
Chalcone/analogs & derivatives*;
Quinones/pharmacology*;
Pyroptosis/drug effects*;
Caspase 1/metabolism*;
Glucose;
Phosphate-Binding Proteins/metabolism*;
Signal Transduction/drug effects*;
Intracellular Signaling Peptides and Proteins/metabolism*;
Oxygen/metabolism*;
Cytokines/metabolism*;
Gasdermins
- From:
Chinese journal of integrative medicine
2024;30(11):1027-1034
- CountryChina
- Language:English
-
Abstract:
OBJECTIVE:To observe the protective effect and mechanism of hydroxyl safflower yellow A (HSYA) from myocardial ischemia-reperfusion injury on human umbilical vein endothelial cells (HUVECs).
METHODS:HUVECs were treated with oxygen-glucose deprivation reperfusion (OGD/R) to simulate the ischemia reperfusion model, and cell counting kit-8 was used to detect the protective effect of different concentrations (1.25-160 µ mol/L) of HSYA on HUVECs after OGD/R. HSYA 80 µ mol/L was used for follow-up experiments. The contents of inflammatory cytokines interleukin (IL)-18, IL-1 β, monocyte chemotactic protein 1 (MCP-1), tumor necrosis factor α (TNF-α) and IL-6 before and after administration were measured by enzyme-linked immunosorbent assay. The protein expressions of toll-like receptor, NOD-like receptor containing pyrin domain 3 (NLRP3), gasdermin D (GSDMD) and GSDMD-N-terminal domain (GSDMD-N) before and after administration were detected by Western blot. NLRP3 inflammasome inhibitor cytokine release inhibitory drug 3 sodium salt (CRID3 sodium salt, also known as MCC950) and agonist were added, and the changes of NLRP3, cysteine-aspartic acid protease 1 (Caspase-1), GSDMD and GSDMD-N protein expressions were detected by Western blot.
RESULTS:HSYA inhibited OGD/R-induced inflammation and significantly decreased the contents of inflammatory cytokines IL-18, IL-1 β, MCP-1, TNF-α and IL-6 (P<0.01 or P<0.05). At the same time, by inhibiting NLRP3/Caspase-1/GSDMD pathway, HSYA can reduce the occurrence of pyroptosis after OGD/R and reduce the expression of NLRP3, Caspase-1, GSDMD and GSDMD-N proteins (P<0.01).
CONCLUSIONS:The protective effect of HSYA on HUVECs after OGD/R is related to down-regulating the expression of NLRP3 inflammasome and inhibiting pyroptosis.
