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
为探究冬虫夏草菌(Ophiocordyceps sinensis)菌丝体氨基酸及其衍生物的差异性,采用超高效液相色谱串联质谱(Ultra performance liquid chromatography,tandem mass spectrometry,UPLC-MS/MS)技术对3株冬虫夏草菌(玉树菌株XSH、达日菌株D...为探究冬虫夏草菌(Ophiocordyceps sinensis)菌丝体氨基酸及其衍生物的差异性,采用超高效液相色谱串联质谱(Ultra performance liquid chromatography,tandem mass spectrometry,UPLC-MS/MS)技术对3株冬虫夏草菌(玉树菌株XSH、达日菌株DR、贵德菌株LJ)菌丝体的氨基酸及其衍生物进行靶向定量检测,利用主成分分析(Principal component analysis,PCA)和正交偏最小二乘判别分析(Orthogonal signal correction and partial least squares-discriminant analysis,OPLS-DA)考察样品分类情况、筛选差异代谢物。结果表明,3株菌株菌丝体中均检测到72种氨基酸及其衍生物,发现除组氨酸外可合成蛋白质的19种氨基酸,菌株XSH的总氨基酸及必需氨基酸绝对含量均高于其他菌株。菌株XSH相比菌株DR和菌株LJ分别含有29种和28种差异氨基酸及其衍生物,菌株DR相比菌株LJ含有10种差异氨基酸及其衍生物,此外,3株菌株菌丝体含有3个共有的差异氨基酸及其衍生物,分别为高精氨酸、N-乙酰-L-谷氨酰胺、肌氨酸。京都基因与基因组百科全书(Kyoto encyclopedia of genes and genomes,KEGG)通路富集分析显示,差异氨基酸及其衍生物在精氨酸和脯氨酸代谢通路中更活跃,不同产区冬虫夏草菌株的氨基酸含量可能受精氨酸和脯氨酸代谢通路的影响。基于研究结果发现不同产区的冬虫夏草菌株的氨基酸及其衍生物存在较大的差异。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.
文摘为探究冬虫夏草菌(Ophiocordyceps sinensis)菌丝体氨基酸及其衍生物的差异性,采用超高效液相色谱串联质谱(Ultra performance liquid chromatography,tandem mass spectrometry,UPLC-MS/MS)技术对3株冬虫夏草菌(玉树菌株XSH、达日菌株DR、贵德菌株LJ)菌丝体的氨基酸及其衍生物进行靶向定量检测,利用主成分分析(Principal component analysis,PCA)和正交偏最小二乘判别分析(Orthogonal signal correction and partial least squares-discriminant analysis,OPLS-DA)考察样品分类情况、筛选差异代谢物。结果表明,3株菌株菌丝体中均检测到72种氨基酸及其衍生物,发现除组氨酸外可合成蛋白质的19种氨基酸,菌株XSH的总氨基酸及必需氨基酸绝对含量均高于其他菌株。菌株XSH相比菌株DR和菌株LJ分别含有29种和28种差异氨基酸及其衍生物,菌株DR相比菌株LJ含有10种差异氨基酸及其衍生物,此外,3株菌株菌丝体含有3个共有的差异氨基酸及其衍生物,分别为高精氨酸、N-乙酰-L-谷氨酰胺、肌氨酸。京都基因与基因组百科全书(Kyoto encyclopedia of genes and genomes,KEGG)通路富集分析显示,差异氨基酸及其衍生物在精氨酸和脯氨酸代谢通路中更活跃,不同产区冬虫夏草菌株的氨基酸含量可能受精氨酸和脯氨酸代谢通路的影响。基于研究结果发现不同产区的冬虫夏草菌株的氨基酸及其衍生物存在较大的差异。
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.
