Objective To explore the anti-inflammatory phytoconstituents from various plant sources as tumour necrosis factor-α(TNF-α)-inhibitor,a mediator involved in the inflammatory disorder,by in silico molecular docking.Me...Objective To explore the anti-inflammatory phytoconstituents from various plant sources as tumour necrosis factor-α(TNF-α)-inhibitor,a mediator involved in the inflammatory disorder,by in silico molecular docking.Methods Based on previous findings,we performed the in silico assessment of anti-inflammatory phytoconstituents from different medicinal plants to understand their binding patterns against TNF-α(PDB ID:6OP0)using AutoDock Vina.Molecular docking was performed by setting a grid box(25×25×25)Åcentered at[-12.817×(-1.618)×19.009]A with 0.375A of grid spacing.Furthermore,Discovery Studio Client 2020 program was utilized to assess two-and three-dimensional(2D and 3D)hydrogen-bond interactions concerning an amino acid of target and ligand.Physicochemical properties were reported using the Lipinski’s rule and SwissADME database to support the in silico findings.Results From the selected medicinal plants,more than 200 phytocompounds were screened against TNF-α protein with binding scores in the range of -12.3 to -2.5 kcal/mol.Amongst them,emodin,aloe-emodin,pongamol,purpuritenin,semiglabrin,ellagic acid,imperatorin,α-tocopherol,and octanorcucurbitacin A showed good binding affinity as -10.6,-10.0,-10.5,-10.1,-11.2,-10.3,-10.1,-10.1,and -10.0 kcal/mol,respectively.Also,the absorption,distribution,metabolism,excretion,and toxicology(ADMET)profiles were well within acceptable limits.Conclusion Based on our preliminary findings,we conclude that the selected phytoconstituents have the potential to be good anti-inflammatory candidates by inhibiting the TNF-α target.These compounds can be further optimized and validated as new therapeutic components to develop more effective and safe anti-inflammatory drugs.展开更多
Inhibition of the enzyme COMT （catechol-O-methyltransferase） is an important approach in the treatment of Parkinson＇s disease. A series of potent catechols for COMT may give insight to develop new ways of antiparki...Inhibition of the enzyme COMT （catechol-O-methyltransferase） is an important approach in the treatment of Parkinson＇s disease. A series of potent catechols for COMT may give insight to develop new ways of antiparkinson drug. COMT inhibitors represent a new class of antiparkinson drugs, when they are coadministered with levodopa. Our goal of research is to study the inhibition of catechol-O-methyltransferase by molecular modeling methods. Different molecular modeling tools are used to perform this work （molecular mechanics, molecular dynamics and molecular docking （molegro virtnaldocker））. The results obtained from this work, into which the inhibition of catechol-O-methyltransferase by molecular modeling methods was elucidated, allow us to conclude that different catechols presents a more optimised inhibition of catechol-O-methyltransferase. The results suggest reducing the severity of Parkinson＇s disease.展开更多
Acute kidney injury(AKI)is a common and serious health issue with a growing incidence and mortality rate.Tripterygium wilfordii(TW)is a traditional Chinese medicine that has been reported to cause kidney damage.Howeve...Acute kidney injury(AKI)is a common and serious health issue with a growing incidence and mortality rate.Tripterygium wilfordii(TW)is a traditional Chinese medicine that has been reported to cause kidney damage.However,the associated mechanism of TW-induced AKI remains unclear.Therefore,we aimed to uncover the associated mechanisms of AKI induced by TW using network pharmacology and bioinformatics.The candidate compounds of TW and the potential targets were screened using TCMSP and CTD database,and the AKI-related targets were identified from the Dis Ge NET database.The disease targets were intersected with the drug targets,and the Wayne diagram was drawn by Venny 2.1.0 software.We developed proteinprotein interactions(PPI)network and the“disease-compound-target-pathway”network through the Cytoscape software.By using the DAVID database,GO and KEGG enrichment analysis was carried out to reveal the potential signaling pathways of the compound-TW-induced AKI.Meanwhile,the Auto dock vina 1.1.2 was used for molecular docking to verify the active compound and key targets’binding ability.Critical compounds and key targets of TW-induced AKI were identified,including triptolide,kaempferol,β-sitosterol,nobiletin,stigmasterol,TNF,and so on.The GO analysis showed that potential genes’biological function was mainly involved in apoptosis,oxidative stress,and inflammation.Moreover,eight signaling pathways were found,including the HIF-1 signaling pathway,VEGF signaling pathway,apoptosis,and so on.The molecular docking results proved that the core compound’s affinity with the corresponding protein of the gene targets was good.This study preliminarily predicted the core toxic compounds,targets,and related pathways of TW-induced AKI,providing a theoretical basis for the follow-up clinical rational drug use and related research work of TW.展开更多
文摘Objective To explore the anti-inflammatory phytoconstituents from various plant sources as tumour necrosis factor-α(TNF-α)-inhibitor,a mediator involved in the inflammatory disorder,by in silico molecular docking.Methods Based on previous findings,we performed the in silico assessment of anti-inflammatory phytoconstituents from different medicinal plants to understand their binding patterns against TNF-α(PDB ID:6OP0)using AutoDock Vina.Molecular docking was performed by setting a grid box(25×25×25)Åcentered at[-12.817×(-1.618)×19.009]A with 0.375A of grid spacing.Furthermore,Discovery Studio Client 2020 program was utilized to assess two-and three-dimensional(2D and 3D)hydrogen-bond interactions concerning an amino acid of target and ligand.Physicochemical properties were reported using the Lipinski’s rule and SwissADME database to support the in silico findings.Results From the selected medicinal plants,more than 200 phytocompounds were screened against TNF-α protein with binding scores in the range of -12.3 to -2.5 kcal/mol.Amongst them,emodin,aloe-emodin,pongamol,purpuritenin,semiglabrin,ellagic acid,imperatorin,α-tocopherol,and octanorcucurbitacin A showed good binding affinity as -10.6,-10.0,-10.5,-10.1,-11.2,-10.3,-10.1,-10.1,and -10.0 kcal/mol,respectively.Also,the absorption,distribution,metabolism,excretion,and toxicology(ADMET)profiles were well within acceptable limits.Conclusion Based on our preliminary findings,we conclude that the selected phytoconstituents have the potential to be good anti-inflammatory candidates by inhibiting the TNF-α target.These compounds can be further optimized and validated as new therapeutic components to develop more effective and safe anti-inflammatory drugs.
文摘Inhibition of the enzyme COMT （catechol-O-methyltransferase） is an important approach in the treatment of Parkinson＇s disease. A series of potent catechols for COMT may give insight to develop new ways of antiparkinson drug. COMT inhibitors represent a new class of antiparkinson drugs, when they are coadministered with levodopa. Our goal of research is to study the inhibition of catechol-O-methyltransferase by molecular modeling methods. Different molecular modeling tools are used to perform this work （molecular mechanics, molecular dynamics and molecular docking （molegro virtnaldocker））. The results obtained from this work, into which the inhibition of catechol-O-methyltransferase by molecular modeling methods was elucidated, allow us to conclude that different catechols presents a more optimised inhibition of catechol-O-methyltransferase. The results suggest reducing the severity of Parkinson＇s disease.
基金The Science Foundation of Health and Family Planning Commission of Jiangxi Province(Grant No.20181140)the Science and Technology Research Project of Jiangxi Provincial Department of Education(Grant No.GJJ201819,180919)。
文摘Acute kidney injury(AKI)is a common and serious health issue with a growing incidence and mortality rate.Tripterygium wilfordii(TW)is a traditional Chinese medicine that has been reported to cause kidney damage.However,the associated mechanism of TW-induced AKI remains unclear.Therefore,we aimed to uncover the associated mechanisms of AKI induced by TW using network pharmacology and bioinformatics.The candidate compounds of TW and the potential targets were screened using TCMSP and CTD database,and the AKI-related targets were identified from the Dis Ge NET database.The disease targets were intersected with the drug targets,and the Wayne diagram was drawn by Venny 2.1.0 software.We developed proteinprotein interactions(PPI)network and the“disease-compound-target-pathway”network through the Cytoscape software.By using the DAVID database,GO and KEGG enrichment analysis was carried out to reveal the potential signaling pathways of the compound-TW-induced AKI.Meanwhile,the Auto dock vina 1.1.2 was used for molecular docking to verify the active compound and key targets’binding ability.Critical compounds and key targets of TW-induced AKI were identified,including triptolide,kaempferol,β-sitosterol,nobiletin,stigmasterol,TNF,and so on.The GO analysis showed that potential genes’biological function was mainly involved in apoptosis,oxidative stress,and inflammation.Moreover,eight signaling pathways were found,including the HIF-1 signaling pathway,VEGF signaling pathway,apoptosis,and so on.The molecular docking results proved that the core compound’s affinity with the corresponding protein of the gene targets was good.This study preliminarily predicted the core toxic compounds,targets,and related pathways of TW-induced AKI,providing a theoretical basis for the follow-up clinical rational drug use and related research work of TW.
