Cucurbitacins mitigate vascular neointimal hyperplasia by suppressing cyclin A2 expression and inhibiting VSMC proliferation  

作　　者：Ruqiang Yuan Lei Qian Hu Xu Weijing Yun 

机构地区：[1]Advanced Institute for Medical Sciences,Dalian Medical University,Dalian,China [2]Health Science Center,East China Normal University,Shanghai,China

出　　处：《Animal Models and Experimental Medicine》2024年第4期397-407,共11页动物模型与实验医学（英文）

基　　金：Scientific Research Fund Project of Liaoning Provincial Department of Education,Grant/Award Number:LJKMZ20221267,LJKZ0840 and LJKZ0847;National Natural Science Foundation of China Grants,Grant/Award Number:81900267。

摘　　要：Background:Restenosis frequently occurs after percutaneous angioplasty in patients with vascular occlusion and seriously threatens their health.Substantial evidence has revealed that preventing vascular smooth muscle cell proliferation using a drug-eluting stent is an effective approach to improve restenosis.Cucurbitacins have been demonstrated to exert an anti-proliferation effect in various tumors and a hypoten-sive effect.This study aims to investigate the role of cucurbitacins extracted from Cucumis melo L.(CuECs)and cucurbitacin B(CuB)on restenosis.Methods:C57BL/6 mice were subjected to left carotid artery ligation and subcu-taneously injected with CuECs or CuB for 4 weeks.Hematoxylin-Eosin,immuno-fluorescence and immunohistochemistry staining were used to evaluate the effect of CuECs and CuB on neointimal hyperplasia.Western blot,real-time PCR,flow cytometry analysis,EdU staining and cellular immunofluorescence assay were em-ployed to measure the effects of CuECs and CuB on cell proliferation and the cell cycle in vitro.The potential interactions of CuECs with cyclin A2 were performed by molecular docking.Results:The results demonstrated that both CuECs and CuB exhibited significant inhibitory effects on neointimal hyperplasia and proliferation of vascular smooth muscle cells.Furthermore,CuECs and CuB mediated cell cycle arrest at the S phase.Autodocking analysis demonstrated that CuB,CuD,CuE and CuI had high binding en-ergy for cyclin A2.Our study also showed that CuECs and CuB dramatically inhibited FBS-induced cyclin A2 expression.Moreover,the expression of cyclin A2 in CuEC-and CuB-treated neointima was downregulated.Conclusions:CuECs,especially CuB,exert an anti-proliferation effect in VSMCs and may be potential drugs to prevent restenosis.

关 键 词：CuB CUCURBITACIN cyclin A2 RESTENOSIS vascular smooth muscle cell 

分 类 号：R285[医药卫生—中药学]