From the seeds of Peganum harmala L.,three new alkaloids ofβ-carboline were isolated.Among them,peganumiums A(1)and B(2)were dimers with specific new scaffolds,all with long conjugated systems.Peganumium A and peganu...From the seeds of Peganum harmala L.,three new alkaloids ofβ-carboline were isolated.Among them,peganumiums A(1)and B(2)were dimers with specific new scaffolds,all with long conjugated systems.Peganumium A and peganumium C(3)were ionic alkaloid salts and peganumium B was a hexacycliccondensed alkaloid.The biosynthetic pathways of the three compounds above were also speculated.A preliminary cytotoxicity assay revealed that peganumium B had strong in vitro antiproliferative ability against a variety of cancer cells.The analysis of^(1)H nuclear magnetic resonance(NMR)metabolomics suggested that the antiproliferative mechanism of peganumium B could be associated with the biosynthesis of phenylalanine,tyrosine and tryptophan,the metabolism of glycine,serine,and threonine,the metabolism of taurine and hypotaurine,and the metabolism of nicotinate and nicotinamide.In addition,peganumium B could reduce the mitochondrial content of body-wall muscle cells of a Caenorhabditis elegans(C.elegans)strain in vivo.展开更多
Peganum harmala L.is a medicinal plant,and its seeds have been used to treat gastrointestinal cancer and malaria for a long time in North-Western China.In the present study,we aimed to probe the potential molecular ta...Peganum harmala L.is a medicinal plant,and its seeds have been used to treat gastrointestinal cancer and malaria for a long time in North-Western China.In the present study,we aimed to probe the potential molecular targets and pharmacological mechanisms of Peganum harmala L.seeds(PHS)on hepatocellular carcinoma(HCC)using network analysis and molecular docking.First,the chemical ingredients of PHS were obtained from TCMID and BATMAN-TCM databases,and the effective ingredients were screened by SwissADME.Furthermore,the target information of the effective ingredients was acquired from PharmMapper and SwissTargetPrediction databases.Secondly,HCC-related targets were obtained from Liverome,DisGeNET,and GeneCards databases.The intersection with the PHS was obtained.The“compounds-targets”was drawn using Cytoscape software,and PPI network diagrams were drawn using their intersection targets.GO analysis and KEGG enrichment analysis were carried out using the DAVID database.Finally,molecular docking was conducted between protein receptors and the active components using AutoDockTools.Our results showed 105 intersection targets of PHS with HCC.Moreover,10 core targets included ALB,AKT1,EGFR,CASP3,SRC,ESR1,MAPK3,MMP9,ANXA5,and MAPK1.Besides,404 GO functional annotations were obtained,including 287 biological processes,37 cell compositions,and 80 molecular functions.In addition,110 signaling molecules and pathways,including chemical oncogene receptors,PI3K-Akt pathway,HCC,and hepatitis B,were identified.The molecular docking results showed that the binding energies of the 10 core targets and the 12 active components were all less than–5 kcal/mol.In conclusion,this study expounded on the“component-target-pathway”interaction mechanism of PHS for the treatment of HCC,and it also provided a scientific basis for the clinical application of PHS.展开更多
基金Financial support from Beijing Natural Science Foundation(No.7232283)。
文摘From the seeds of Peganum harmala L.,three new alkaloids ofβ-carboline were isolated.Among them,peganumiums A(1)and B(2)were dimers with specific new scaffolds,all with long conjugated systems.Peganumium A and peganumium C(3)were ionic alkaloid salts and peganumium B was a hexacycliccondensed alkaloid.The biosynthetic pathways of the three compounds above were also speculated.A preliminary cytotoxicity assay revealed that peganumium B had strong in vitro antiproliferative ability against a variety of cancer cells.The analysis of^(1)H nuclear magnetic resonance(NMR)metabolomics suggested that the antiproliferative mechanism of peganumium B could be associated with the biosynthesis of phenylalanine,tyrosine and tryptophan,the metabolism of glycine,serine,and threonine,the metabolism of taurine and hypotaurine,and the metabolism of nicotinate and nicotinamide.In addition,peganumium B could reduce the mitochondrial content of body-wall muscle cells of a Caenorhabditis elegans(C.elegans)strain in vivo.
基金The National Natural Science Foundation of China(Grant No.81760637,81460539)the National Natural Science Foundation of Xinjiang(Grant No.2017D01C207)+1 种基金the Open Research Fund of Xinjiang Uygur Autonomous Region Key Laboratory(Grant No.XJDX1713)。
文摘Peganum harmala L.is a medicinal plant,and its seeds have been used to treat gastrointestinal cancer and malaria for a long time in North-Western China.In the present study,we aimed to probe the potential molecular targets and pharmacological mechanisms of Peganum harmala L.seeds(PHS)on hepatocellular carcinoma(HCC)using network analysis and molecular docking.First,the chemical ingredients of PHS were obtained from TCMID and BATMAN-TCM databases,and the effective ingredients were screened by SwissADME.Furthermore,the target information of the effective ingredients was acquired from PharmMapper and SwissTargetPrediction databases.Secondly,HCC-related targets were obtained from Liverome,DisGeNET,and GeneCards databases.The intersection with the PHS was obtained.The“compounds-targets”was drawn using Cytoscape software,and PPI network diagrams were drawn using their intersection targets.GO analysis and KEGG enrichment analysis were carried out using the DAVID database.Finally,molecular docking was conducted between protein receptors and the active components using AutoDockTools.Our results showed 105 intersection targets of PHS with HCC.Moreover,10 core targets included ALB,AKT1,EGFR,CASP3,SRC,ESR1,MAPK3,MMP9,ANXA5,and MAPK1.Besides,404 GO functional annotations were obtained,including 287 biological processes,37 cell compositions,and 80 molecular functions.In addition,110 signaling molecules and pathways,including chemical oncogene receptors,PI3K-Akt pathway,HCC,and hepatitis B,were identified.The molecular docking results showed that the binding energies of the 10 core targets and the 12 active components were all less than–5 kcal/mol.In conclusion,this study expounded on the“component-target-pathway”interaction mechanism of PHS for the treatment of HCC,and it also provided a scientific basis for the clinical application of PHS.
