Ginkgo biloba L.leaf(GBL)has been reported to protect against ischemic stroke(IS),one of the leading causes of death and longterm disability worldwide,while there is a lack of systematic study on the exact mechanism.H...Ginkgo biloba L.leaf(GBL)has been reported to protect against ischemic stroke(IS),one of the leading causes of death and longterm disability worldwide,while there is a lack of systematic study on the exact mechanism.Here,network pharmacology and bioinformatics were used to predict the active components,important targets,and potential mechanisms of GBL in the treatment of IS.Active compounds of GBL were screened based on drug-like index and oral bioavailability,key target genes were screened based on network pharmacology and gene chip,downstream pathways for the regulation of key target genes were predicted based on gene set enrichment analysis,and the interaction between key targets and active compounds was verified based on molecular docking.The results showed that GBL played a protective role in cerebral ischemia with mainly 14 active compounds,such as isoquercitrin,luteolin-4’-glucoside,beta-sitosterol,campesterol,diosmetin,ginkgolide B,ginkgolide C,ginkgolide J,ginkgolide M,isogoycyrol,laricitrin,luteolin,sesamin,and stigmasterol.Further studies revealed that GBL played important role in immunomodulation and inflammation inhibition after cerebral ischemia by acting on its peripheral targets ARG1 and MMP9 to regulate Toll-like receptor,Chemokine and Notch signaling pathway.Meanwhile,GBL played important role in reducing neuroinflammation and blood-brain barrier damage after cerebral ischemia by acting on its central targets,CCL2,PTGS2,IL6,IL1B and MMP9 to regulate the Cytokine-cytokine receptor interaction,Jak-STAT,and Toll-like receptor signaling pathway.Additionally,molecular docking verified that the active compounds mentioned above could bind to ARG1,MMP9,CCL2,PTGS2,IL6,and IL1B.The present study shows the multicomponent,multitarget and multichannel pharmacological effects of GBL on cerebral ischemia and provides a new strategy for the treatment of IS.展开更多
基金supported by the National Natural Science Foundation of China(82074056).
文摘Ginkgo biloba L.leaf(GBL)has been reported to protect against ischemic stroke(IS),one of the leading causes of death and longterm disability worldwide,while there is a lack of systematic study on the exact mechanism.Here,network pharmacology and bioinformatics were used to predict the active components,important targets,and potential mechanisms of GBL in the treatment of IS.Active compounds of GBL were screened based on drug-like index and oral bioavailability,key target genes were screened based on network pharmacology and gene chip,downstream pathways for the regulation of key target genes were predicted based on gene set enrichment analysis,and the interaction between key targets and active compounds was verified based on molecular docking.The results showed that GBL played a protective role in cerebral ischemia with mainly 14 active compounds,such as isoquercitrin,luteolin-4’-glucoside,beta-sitosterol,campesterol,diosmetin,ginkgolide B,ginkgolide C,ginkgolide J,ginkgolide M,isogoycyrol,laricitrin,luteolin,sesamin,and stigmasterol.Further studies revealed that GBL played important role in immunomodulation and inflammation inhibition after cerebral ischemia by acting on its peripheral targets ARG1 and MMP9 to regulate Toll-like receptor,Chemokine and Notch signaling pathway.Meanwhile,GBL played important role in reducing neuroinflammation and blood-brain barrier damage after cerebral ischemia by acting on its central targets,CCL2,PTGS2,IL6,IL1B and MMP9 to regulate the Cytokine-cytokine receptor interaction,Jak-STAT,and Toll-like receptor signaling pathway.Additionally,molecular docking verified that the active compounds mentioned above could bind to ARG1,MMP9,CCL2,PTGS2,IL6,and IL1B.The present study shows the multicomponent,multitarget and multichannel pharmacological effects of GBL on cerebral ischemia and provides a new strategy for the treatment of IS.
