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Crosstalk among Oxidative Stress,Autophagy,and Apoptosis in the Protective Effects of Ginsenoside Rb1 on Brain Microvascular Endothelial Cells:A Mixed Computational and Experimental Study

摘要Objective:Brain microvascular endothelial cells(BMECs)were found to shift from their usually inactive state to an active state in ischemic stroke(IS)and cause neuronal damage.Ginsenoside Rb1(GRb1),a component derived from medicinal plants,is known for its pharmacological benefits in IS,but its protective effects on BMECs have yet to be explored.This study aimed to investigate the potential protective effects of GRb1 on BMECs.Methods:An in vitro oxygen-glucose deprivation/reperfusion(OGD/R)model was established to mimic ischemia-reperfusion(I/R)injury.Bulk RNA-sequencing data were analyzed by using the Human Autophagy Database and various bioinformatic tools,including gene set enrichment analysis(GSEA),Gene Ontology(GO)classification and enrichment analysis,Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis,protein-protein interaction network analysis,and molecular docking.Experimental validation was also performed to ensure the reliability of our findings.Results:Rb1 had a protective effect on BMECs subjected to OGD/R injury.Specifically,GRbl was found to modulate the interplay between oxidative stress,apoptosis,and autophagy in BMECs.Key targets such as sequestosome 1(SQSTM1/p62),autophagy related 5(ATG5),and hypoxia-inducible factor 1-alpha(HIF-1α)were identified,highlighting their potential roles in mediating the protective effects of GRbl against IS-induced damage.Conclusion:GRb1 protects BMECs against OGD/R injury by influencing oxidative stress,apoptosis,and autophagy.The identification of SQSTM1/p62,ATG5,and HIF-1α as promising targets further supports the potential of GRb1 as a therapeutic agent for IS,providing a foundation for future research into its mechanisms and applications in IS treatment.

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作者 Yi-miao LUO [1] Shu-sen LIU [2] Ming ZHAO [3] Wei WEI [4] Jiu-xiu YAO [4] Jia-hui SUN [4] Yu CAO [3] Hao LI [5] 学术成果认领
作者单位 Department of Geriatrics,Peking University Traditional Chinese Medicine Clinical Medical School(Xiyuan),Beijing 100901,China;Department of Integration of Chinese and Western Medicine,Peking University Health Science Center,Beijing 100191,China [1] School of Pharmacy,Harbin University of Commerce,Harbin 150028,China [2] Xiyuan Hospital,China Academy of Chinese Medical Science,Beijing 100901,China [3] Wangjing Hospital,China Academy of Chinese Medical Science,Beijing 100102,China [4] Department of Geriatrics,Peking University Traditional Chinese Medicine Clinical Medical School(Xiyuan),Beijing 100901,China;Department of Integration of Chinese and Western Medicine,Peking University Health Science Center,Beijing 100191,China;Wangjing Hospital,China Academy of Chinese Medical Science,Beijing 100102,China [5]
栏目名称 ORIGINAL ARTICLES
DOI 10.1007/s11596-024-2858-2
发布时间 2024-07-18
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