Mechanism of ginkgolide B antagonizing vascular endothelial injury by inhibiting endoplasmic reticulum stress
10.3969/j.issn.1006-5725.2023.24.005
- VernacularTitle:银杏内酯B通过抑制内质网应激拮抗血管内皮损伤的作用机制
- Author:
Changsong MA
1
;
Shuai HUANG
;
Qingde WA
;
Weizhi CHEN
;
Yang WANG
;
Xitao LINGHU
;
Yubo TANG
Author Information
1. 广州医科大学附属第二医院骨科(广州 510230)
- Keywords:
ginkgolide B;
endoplasmic reticulum stress;
vascular endothelial injury;
mitochondrial disorder;
bone repair
- From:
The Journal of Practical Medicine
2023;39(24):3175-3181
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the potential of ginkgolide B(GB)in mitigating vascular endothelial injury by antagonizing endoplasmic reticulum stress(ERS)and elucidate its underlying molecular mechanism.Methods An injury model of human bone marrow-derived endothelial progenitor cells(EPCs)induced by tunica-mycin(TM)was established.Cell proliferation was assessed using MTS assay,while cell viability was determined through Calcein-AM/EthD-I double staining.Transwell assay was employed to evaluate cell migration ability.DCFH-DA staining was utilized to measure intracellular ROS levels,and NADPH activity was quantified via ELISA.JC-1 and DiOC6 staining were performed for qualitative and quantitative assessment of mitochondrial membrane potential respectively.Qrt-pcr analysis was conducted to determine mRNA expression levels,whereas western blot analysis enabled detection of protein expression levels in the cells.Results GB dose-dependently attenuated tunicamycin-induced ERS-mediated endothelial injury in hEPCs,as evidenced by decreased cell viability,impaired cell migration,and angiogenesis inhibition(P<0.01).Furthermore,GB treatment significantly reduced ROS production and NADPH levels within the cells(P<0.01),while also inhibiting ERS-mediated decline in mitochondrial membrane potential concentration-dependently(P<0.01).Additionally,GB inhibited the expression of ERS-related proteins such as GRP78,ATF4,CHOP etc.,regulated apoptosis-related protein Bcl-xl,Bax cleaved caspase-4 cytochrome c;thereby effectively counteracting endoplasmic reticulum stress-induced cellular damage.Conclusions GB exerts a protective effect on vascular endothelium by antagonizing endoplasmic reticulum stress;this mechanism may be attributed to its ability to reduce intracellular reactive oxygen species levels.It also suppresses the expression of ERS-related proteins(CHOP78 and ATF4),and modulates apoptosis-associated proteins(Bcl-xl,Bax,cleaved caspase-4,and cytochrome c).
