Objective:To explore the therapeutic potential of Cordyceps sinensis(Berk.)Sacc.(C.sinensis,Dong Chong Xia Cao)in an ischemic stroke(IS)model and predict its possible mechanism through network pharmacology.Methods:Thi...Objective:To explore the therapeutic potential of Cordyceps sinensis(Berk.)Sacc.(C.sinensis,Dong Chong Xia Cao)in an ischemic stroke(IS)model and predict its possible mechanism through network pharmacology.Methods:Thirty-three SpragueeDawley rats were randomly divided into the Sham,model,and C.sinensis groups.After 5 days of pre-treatment,the model group and the C.sinensis group were sub-jected to middle cerebral artery occlusion(MCAO)modeling.Effect of C.sinensis on MCAO rats was evaluated by comparing cerebral infarct size,neurological function,cerebral water content,pathological changes,and certain biochemical indicators.Intersection targets between C.sinensis and IS was screened using network pharmacology analysis.Relationship among core components,targets and pathways of C.sinensis in treating IS was constructed through network pharmacology analysis and further verified by molecular docking.Finally,the DAVID v8.8 database was used for performing GO analysis and KEGG pathway enrichment analysis by importing the intersection targets.Results:Compared with the model group,C.sinensis significantly reduced the volume of cerebral infarction(P=0.026),the cerebral water content(P¼.0013),the mNSS score(P<0.001),and the levels of IL-17(P=0.031),TNF-α(P=0.016),MDA(P=0.014),and glutamate(P=0.014)in serum,while upregulating the level of SOD in serum and improving the pathological morphology in MCAO rat ischemic brains.The results of network pharmacology analysis showed that core targets(such as CASP3,PTGS2,and PPARG)and the main enrichment pathways(IL-17,AGE-RAGE,and TNF signaling pathways)were regulated by 30 chemical components of C.sinensis,which effectively treated IS in MCAO rats.Conclusion:The results of this study showed that C.sinensis effectively interfered with MCAO rats,and the mechanism may be related to the regulation of blood lipids and to anti-apoptosis and anti-inflammatory effects.展开更多
Background:The present study intented to delve into the molecular mechanism of Cordyceps sinensis(C.sinensis)in treating atherosclerosis by combining network pharmacology and molecular docking analysis.Methods:We sear...Background:The present study intented to delve into the molecular mechanism of Cordyceps sinensis(C.sinensis)in treating atherosclerosis by combining network pharmacology and molecular docking analysis.Methods:We searched the databases including Traditional Chinese Medicines Systems Pharmacology Database and Analysis Platform,PubChem,and PharmMapper to screen out the active chemical ingredients of C.sinensis and the corresponding targets.The String database was used for the matching normalization of results,and the software Cytoscape 3.7.2 was adopted to establish the C.sinensis-active components-targets of action-disease network.The databases of Online Mendelian Inheritance in Man database,GeneCards,Therapeutic Target Database,and DisGNET were searched to yield the major targets of atherosclerosis(AS),which were matched with the active component targets of C.sinensis to identify the potential therapeutic targets.The String database was utilized to set up the protein-protein interaction network,and Cytoscape software was applied for topological analysis,which was followed by the Gene Ontology analysis and Kyoto Encyclopedia of Genes and Genomes signaling pathway analysis based on the DAVID database.Finally,the core components of C.sinensis and the targets of action were confirmed via molecular docking on AutoDock Vina and PyMOL.Results:In total,7 bioactive ingredients of C.sinensis were identified from Traditional Chinese Medicines Systems Pharmacology Database and Analysis Platform database and 319 predicted targets were obtained,231 of which were associated with AS.The core targets involved in AS treatment with C.sinensis included MAPK1,SRC,PIK3R1,AKT1,and HSP90AA1.The enrichment analysis unveiled the primary pathways involved in these processes,such as pathways in cancer and lipid and atherosclerosis.Moreover,through molecular docking,it was found that the active ingredients of C.sinensis presented with strong binding capacities with their corresponding targets,and the strongest binding capacity was observed between peroxyergosterol and SRC.Conclusions:The present study revealed at the molecular level that C.sinensis played its role in AS treatment through multiple drug active components,targets of action and pathways,which would point out the direction and provide theoretic basis for future research.展开更多
基金This study was supported by Key Project at Central Government Level:The Ability Establishment of Sustainable Use for Valuable Chinese Medicine Resources(2060302).
文摘Objective:To explore the therapeutic potential of Cordyceps sinensis(Berk.)Sacc.(C.sinensis,Dong Chong Xia Cao)in an ischemic stroke(IS)model and predict its possible mechanism through network pharmacology.Methods:Thirty-three SpragueeDawley rats were randomly divided into the Sham,model,and C.sinensis groups.After 5 days of pre-treatment,the model group and the C.sinensis group were sub-jected to middle cerebral artery occlusion(MCAO)modeling.Effect of C.sinensis on MCAO rats was evaluated by comparing cerebral infarct size,neurological function,cerebral water content,pathological changes,and certain biochemical indicators.Intersection targets between C.sinensis and IS was screened using network pharmacology analysis.Relationship among core components,targets and pathways of C.sinensis in treating IS was constructed through network pharmacology analysis and further verified by molecular docking.Finally,the DAVID v8.8 database was used for performing GO analysis and KEGG pathway enrichment analysis by importing the intersection targets.Results:Compared with the model group,C.sinensis significantly reduced the volume of cerebral infarction(P=0.026),the cerebral water content(P¼.0013),the mNSS score(P<0.001),and the levels of IL-17(P=0.031),TNF-α(P=0.016),MDA(P=0.014),and glutamate(P=0.014)in serum,while upregulating the level of SOD in serum and improving the pathological morphology in MCAO rat ischemic brains.The results of network pharmacology analysis showed that core targets(such as CASP3,PTGS2,and PPARG)and the main enrichment pathways(IL-17,AGE-RAGE,and TNF signaling pathways)were regulated by 30 chemical components of C.sinensis,which effectively treated IS in MCAO rats.Conclusion:The results of this study showed that C.sinensis effectively interfered with MCAO rats,and the mechanism may be related to the regulation of blood lipids and to anti-apoptosis and anti-inflammatory effects.
基金supported by the Educational Commission of Hubei Province of China(D20222802).
文摘Background:The present study intented to delve into the molecular mechanism of Cordyceps sinensis(C.sinensis)in treating atherosclerosis by combining network pharmacology and molecular docking analysis.Methods:We searched the databases including Traditional Chinese Medicines Systems Pharmacology Database and Analysis Platform,PubChem,and PharmMapper to screen out the active chemical ingredients of C.sinensis and the corresponding targets.The String database was used for the matching normalization of results,and the software Cytoscape 3.7.2 was adopted to establish the C.sinensis-active components-targets of action-disease network.The databases of Online Mendelian Inheritance in Man database,GeneCards,Therapeutic Target Database,and DisGNET were searched to yield the major targets of atherosclerosis(AS),which were matched with the active component targets of C.sinensis to identify the potential therapeutic targets.The String database was utilized to set up the protein-protein interaction network,and Cytoscape software was applied for topological analysis,which was followed by the Gene Ontology analysis and Kyoto Encyclopedia of Genes and Genomes signaling pathway analysis based on the DAVID database.Finally,the core components of C.sinensis and the targets of action were confirmed via molecular docking on AutoDock Vina and PyMOL.Results:In total,7 bioactive ingredients of C.sinensis were identified from Traditional Chinese Medicines Systems Pharmacology Database and Analysis Platform database and 319 predicted targets were obtained,231 of which were associated with AS.The core targets involved in AS treatment with C.sinensis included MAPK1,SRC,PIK3R1,AKT1,and HSP90AA1.The enrichment analysis unveiled the primary pathways involved in these processes,such as pathways in cancer and lipid and atherosclerosis.Moreover,through molecular docking,it was found that the active ingredients of C.sinensis presented with strong binding capacities with their corresponding targets,and the strongest binding capacity was observed between peroxyergosterol and SRC.Conclusions:The present study revealed at the molecular level that C.sinensis played its role in AS treatment through multiple drug active components,targets of action and pathways,which would point out the direction and provide theoretic basis for future research.
