Objective To explore the molecular targets and associated potential pathways of Lycii Fructus(LF,Gou Qi Zi,枸杞子)in the treatment of retinitis pigmentosa(RP)by the approaches of network pharmacology and bioinformatic...Objective To explore the molecular targets and associated potential pathways of Lycii Fructus(LF,Gou Qi Zi,枸杞子)in the treatment of retinitis pigmentosa(RP)by the approaches of network pharmacology and bioinformatics.Methods The potential blood-entry active ingredients and targets of LF were retrieved by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP).RP-related gene targets were retrieved through disease comprehensive databases.Protein-protein interaction(PPI)network of LF component-targets and RP disease-targets was constructed by STRING,and the intersection of the 2 networks was extracted.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis of theintersection network were conducted by Database for Annotation,Visualization and Integrated Discovery(DAVID).CytoHubba was used to screen the key targets.Results A total of 188 chemical constituents related to LF was retrieved from TCMSP database.45 active ingredients were screened according to pharmacokinetic parameters oral bioavailability(OB)and drug similarity(DL).36 active ingredients were further screened and 201 targets related to these constituents were obtained.206 target genes directly related to RP were obtained from the disease comprehensive databases,and 89 genes were obtained from the intersection of componenttarget and disease-target PPI network.These genes were mainly involved in intracellular signal transduction,GTPase activity regulation,cell morphology regulation,and other biological processes.Molecular functions were mainly related to Rho guanine nucleotide exchange factor activity,GTPase activator activity,receptor signal protein serine/threonine kinase activity and so on.They were enriched in the cytoplasm,cell membrane,Golgi apparatus,and other regions.The mechanism was related to cell cycle pathways,neurotrophin signaling pathways,Ras signaling pathways,and so on.10 key gene targets of LF in the treatment of RP were screened.Conclusions The material basis for LF to exert its pharmacodynamic effect is 36 active ingredients such as cycloartenol,mandenol,and so on.The key targets of LF in the treatment of RP include 10 genes,such as Rho,PAK,and so on.The main mechanism is related to the regulation of the Ras signaling pathway,neurotrophin signaling pathway,cell cycle related pathway,and other signaling networks.展开更多
Objective:To explore the pharmacological basis of the Compound Xintahua (XTH) action in Atherosclerosis (AS) therapy, a network interaction analysis was conducted at the molecular level. Methods:TCMSP database and lit...Objective:To explore the pharmacological basis of the Compound Xintahua (XTH) action in Atherosclerosis (AS) therapy, a network interaction analysis was conducted at the molecular level. Methods:TCMSP database and literature mining were used to analyze the main effective components in XTH, and the targets were predicted by Swiss Target Prediction server according to AS mechanism. The potential targets were introduced into the FunRich database for target annotation and analysis, the path analysis was finally performed based on the FunRich databases. To determine the mechanism of action of XTH. Results:A total of 316 compounds, 117 targets, and 290 signaling pathways were identified. And 16 effective compounds, 39 common targets, and 43 pathways were associated with AS. Conclusions:The results showed that the flavonoids, phenols, organic acids and terpenoids of XTH could participate in the process of lipid metabolism, angiogenesis, oxidation, inflammation, endocrine metabolism, cell proliferation and apoptosis, It was further found that they could play the role of anti-Atherosclerosis through multi-component, multi-target, and multi-channel synergistically.展开更多
Objective The objective of this study was to clarify the potential mechanism of quercetin against knee osteoarthritis(KOA)based on network pharmacology and molecular docking.Methods The targets of quercetin were predi...Objective The objective of this study was to clarify the potential mechanism of quercetin against knee osteoarthritis(KOA)based on network pharmacology and molecular docking.Methods The targets of quercetin were predicted by PubChem and Swiss Target Prediction databases,and the targets of KOA were obtained by DisGeNET,OMIM,and GeneCards databases.Then,the targets of quercetin and KOA were intersected to find the potential targets of quercetin against KOA.The protein–protein interaction network was constructed through the STRING database,and the core targets were screened.Gene ontology(GO)functions enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were performed using DAVID database.The drug–target–pathway–disease network was constructed by Cytoscape software,and the molecular docking verification was performed by Vina.Results There were 49 potential targets for quercetin against KOA,including 10 core targets.GO functions enrichment analysis showed that the biological process of quercetin against KOA mainly involved the negative regulation of apoptotic process,collagen catabolic process,and extracellular matrix disassembly.KEGG pathway enrichment analysis showed that quercetin against KOA was closely related to PI3K-Akt signaling pathway,Rap 1 signaling pathway,FoxO signaling pathway,Ras signaling pathway,TNF signaling pathway,and ErbB signaling pathway.The results of molecular docking showed that the binding energies between ligand and receptors were less than−5 kcal·mol−1.Conclusions The molecular mechanism of quercetin against KOA involves many targets and pathways,which can regulate the proliferation and apoptosis of chondrocytes,degradation of extracellular matrix,and inflammatory reaction.Quercetin can stably bind to the active pockets of core target proteins,thereby exerting the effect against KOA.展开更多
基金funding support from the National Natural Science Foundation of China (No. 81804150 and No. 81703920)Project funded by China Postdoctoral Science Foundation (No. 2019M662790)+4 种基金Natural Science Foundation of Hunan Province, China (No. 2019JJ50442 and No. 2019JJ40226)Research-based Learning and Innovative Experiment Program Project for Hunan University Students (No. 2017280)Scientific Research Project of Hunan Traditional Chinese Medicine Administration (No. 201780)Open Fund Project of Hunan Provincial Key Laboratory for Prevention and Treatment of Ophthalmology and Otolaryngology Diseases with Chinese Medicine (No. 2018YZD05)Open Fund of the Domestic First-class Discipline Construction Project of Chinese Medicine of Hunan University of Chinese Medicine (No. 2018ZYX20 and No. 2018ZYX26)
文摘Objective To explore the molecular targets and associated potential pathways of Lycii Fructus(LF,Gou Qi Zi,枸杞子)in the treatment of retinitis pigmentosa(RP)by the approaches of network pharmacology and bioinformatics.Methods The potential blood-entry active ingredients and targets of LF were retrieved by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP).RP-related gene targets were retrieved through disease comprehensive databases.Protein-protein interaction(PPI)network of LF component-targets and RP disease-targets was constructed by STRING,and the intersection of the 2 networks was extracted.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis of theintersection network were conducted by Database for Annotation,Visualization and Integrated Discovery(DAVID).CytoHubba was used to screen the key targets.Results A total of 188 chemical constituents related to LF was retrieved from TCMSP database.45 active ingredients were screened according to pharmacokinetic parameters oral bioavailability(OB)and drug similarity(DL).36 active ingredients were further screened and 201 targets related to these constituents were obtained.206 target genes directly related to RP were obtained from the disease comprehensive databases,and 89 genes were obtained from the intersection of componenttarget and disease-target PPI network.These genes were mainly involved in intracellular signal transduction,GTPase activity regulation,cell morphology regulation,and other biological processes.Molecular functions were mainly related to Rho guanine nucleotide exchange factor activity,GTPase activator activity,receptor signal protein serine/threonine kinase activity and so on.They were enriched in the cytoplasm,cell membrane,Golgi apparatus,and other regions.The mechanism was related to cell cycle pathways,neurotrophin signaling pathways,Ras signaling pathways,and so on.10 key gene targets of LF in the treatment of RP were screened.Conclusions The material basis for LF to exert its pharmacodynamic effect is 36 active ingredients such as cycloartenol,mandenol,and so on.The key targets of LF in the treatment of RP include 10 genes,such as Rho,PAK,and so on.The main mechanism is related to the regulation of the Ras signaling pathway,neurotrophin signaling pathway,cell cycle related pathway,and other signaling networks.
文摘Objective:To explore the pharmacological basis of the Compound Xintahua (XTH) action in Atherosclerosis (AS) therapy, a network interaction analysis was conducted at the molecular level. Methods:TCMSP database and literature mining were used to analyze the main effective components in XTH, and the targets were predicted by Swiss Target Prediction server according to AS mechanism. The potential targets were introduced into the FunRich database for target annotation and analysis, the path analysis was finally performed based on the FunRich databases. To determine the mechanism of action of XTH. Results:A total of 316 compounds, 117 targets, and 290 signaling pathways were identified. And 16 effective compounds, 39 common targets, and 43 pathways were associated with AS. Conclusions:The results showed that the flavonoids, phenols, organic acids and terpenoids of XTH could participate in the process of lipid metabolism, angiogenesis, oxidation, inflammation, endocrine metabolism, cell proliferation and apoptosis, It was further found that they could play the role of anti-Atherosclerosis through multi-component, multi-target, and multi-channel synergistically.
基金funded by the Project of Chinese Medicine Science and Technology Development Planning in Shandong Province(2017-018)the Project of Scientific Research and Development Plan of Colleges and Universities in Shandong Province(J18KB130)the Project of the First Batch of Excellent Scientific Research and Innovation Team in Shandong University of Chinese Medicine(220316).
文摘Objective The objective of this study was to clarify the potential mechanism of quercetin against knee osteoarthritis(KOA)based on network pharmacology and molecular docking.Methods The targets of quercetin were predicted by PubChem and Swiss Target Prediction databases,and the targets of KOA were obtained by DisGeNET,OMIM,and GeneCards databases.Then,the targets of quercetin and KOA were intersected to find the potential targets of quercetin against KOA.The protein–protein interaction network was constructed through the STRING database,and the core targets were screened.Gene ontology(GO)functions enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were performed using DAVID database.The drug–target–pathway–disease network was constructed by Cytoscape software,and the molecular docking verification was performed by Vina.Results There were 49 potential targets for quercetin against KOA,including 10 core targets.GO functions enrichment analysis showed that the biological process of quercetin against KOA mainly involved the negative regulation of apoptotic process,collagen catabolic process,and extracellular matrix disassembly.KEGG pathway enrichment analysis showed that quercetin against KOA was closely related to PI3K-Akt signaling pathway,Rap 1 signaling pathway,FoxO signaling pathway,Ras signaling pathway,TNF signaling pathway,and ErbB signaling pathway.The results of molecular docking showed that the binding energies between ligand and receptors were less than−5 kcal·mol−1.Conclusions The molecular mechanism of quercetin against KOA involves many targets and pathways,which can regulate the proliferation and apoptosis of chondrocytes,degradation of extracellular matrix,and inflammatory reaction.Quercetin can stably bind to the active pockets of core target proteins,thereby exerting the effect against KOA.
