Scutellarin exerts protective effects against atherosclerosis by regulating PERK-Nrf2/ATF4-CHOP signaling pathways
10.12360/CPB202409056
- VernacularTitle:灯盏花乙素调控PERK-Nrf2/ATF4-CHOP信号通路抗大鼠动脉粥样硬化的分子机制
- Author:
Shi-qi SHAN
1
;
Rui-qi ZHAO
1
;
Yue JIN
1
Author Information
1. 大连医科大学药学院,辽宁大连 116044
- Publication Type:Journal Article
- Keywords:
atherosclerosis;
scutellarin;
endoplasmic reticulum stress;
apoptosis;
Nrf2;
PERK
- From:
Chinese Pharmacological Bulletin
2025;41(4):738-745
- CountryChina
- Language:Chinese
-
Abstract:
Aim To investigate the effect of synthetic small interfering RNA(siRNA)targetingβ-arrestin2 on the apoptosis of hepatic stellate cells(HSC)in vitro.Methods The protective effect of scutellarin on high-fat diet and vitamin D3-induced AS rats.Forty male SD rats weighing 180～220 g were randomly divided into the normal group,the high-fat diet group and the low and high-dose scutellarin.A week of adaptive feeding later,the normal group ate normal diet,the oth-er groups ate a high-fat diet and intraperitoneal injec-tion of vitamin D3,while the administration group was intraperitoneally injected with different doses of scutel-larin daily.The animals were anesthetized after 12 weeks,and the rat aortic blood and aortic blood vessels were taken out.Rat aortic blood vessels were stained with hematoxylin-eosin(HE)to observe the pathologi-cal changes.Tissue superoxide dismutase(SOD),ma-londialdehyde(MDA),glutathione peroxidase(GSH-Px)and glutathione-sulfase(GSH-ST)and total cho-lesterol(TC)),the content of triglyceride(TG),low density lipoprotein(LDL-C),high density lipoprotein(HDL-C)were detected.The mRNA expression of PERK and eIF2α in tissues was detected by qRT-PCR.The expressions of GRP78,p-PERK,PERK,p-eIF2α,eIF2α,ATF4,CHOP,Nrf2,Bcl-2,PUMA,caspase-3 and caspase-12 were detected by Western blot.Re-sults The results of HE staining showed that the foam cells and lipid deposition under the intima of the scute-llarin group were reduced,which proved that scutellarin had a certain protective effect on vascular endothelial cells.In vivo the expression of TC,TG and LDL-C in scutellarin group decreased and the expression of HDL-C increased.Scutellarin could down-regulate the pro-tein expression of PERK and eIF2α,and down-regulate the expression of GRP78,p-PERK,p-eIF2α,ATF4,CHOP,PUMA,caspase-3,caspase-12 and up-regulated Nrf2 and Bcl-2.The anti-AS effect of scutellarin was proved to be closely related to its regulation of PERK-Nrf2/ATF4-CHOP signaling pathway.Conclusion Scutellarin inhibits endoplasmic reticulum stress and apoptosis by regulating the PERK-Nrf2/ATF4-CHOP signaling pathway,thereby treating AS.
