OBJECTIVE:To evaluate the effects of Huangqi(Radix Astragali Mongolici)-Ezhu(Rhizoma Curcumae Phaeocaulis)(HQEZ)on colorectal cancer therapies and to elucidate the potential mechanisms of HQEZ,especially in combinatio...OBJECTIVE:To evaluate the effects of Huangqi(Radix Astragali Mongolici)-Ezhu(Rhizoma Curcumae Phaeocaulis)(HQEZ)on colorectal cancer therapies and to elucidate the potential mechanisms of HQEZ,especially in combination with 5-Fluorouracil(5-FU).METHODS:The anti-tumor effects of HQEZ were evaluated in colorectal cancer models both in vivo and in vitro.The network pharmacological assay was used to investigate potential mechanisms of HQEZ.Potential target genes were selected by Gene Ontology(GO)enrichment analysis,Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis,protein-protein interaction network(PPI)and molecular docking.Within key targets,potential targets related to drug sensitivity,especially the sensitivity to 5-FU,were evaluated in HCT116 in vitro by immunofluorescence,quantitative real-time polymerase chain reaction(qPCR)and Western-blot.Then,changes in potential targets were assessed in tumors from tumor-bearing mice and the expression of these targets was also evaluated in colorectal cancer(COAD)patients from the Cancer Genome Atlas Program(TCGA)database.RESULTS:HQEZ significantly enhanced the anti-tumor activity of 5-FU in vivo and inhibit the growth of HCT116 in vitro.By network pharmacological analysis,key targets,such as protein kinase B(AKT1),epidermal growth factor receptor(EGFR),adenosine triphosphate(ATP)binding cassette subfamily B member 1(ABCB1,also named multidrug resistance protein 1,MDR1),ATP binding cassette subfamily G member 2(ABCG2),thymidylate synthetase(TYMS,also named TS),prostaglandinendoperoxide synthase 2(PTGS2),matrix metallopeptidase 2(MMP2),MMP9,toll like receptor 4(TLR4),TLR9 and dihydropyrimidine dehydrogenase(DPYD),were identified.Additionally,4 potential core active ingredients(Folate,Curcumin,quercetin and kaempferol)were identified to be important for the treatment of colorectal cancer with HQEZ.In key targets,chemoresistance related targets were validated to be affected by HQEZ.Furthermore,5-FU sensitivity related targets,including MDR1,TS,EGFR,ribonucleotide reductase catalytic subunit M1,Breast and Ovarian Cancer Susceptibility Protein 1(BRCA1)and mutl homolog 1 were also significantly reduced by HQEZ both in vitro and in vivo.Finally,these validated key targets and 5-FU sensitivity related targets were demonstrated to be up-regulated in COAD patients based on TCGA database.CONCLUSION:HQEZ has synergistic effects on the antitumor activity of 5-FU in the treatment of colorectal cancer both in vivo and in vitro.The beneficial effect of HQEZ results from the inhibition of the drug sensitivity targets associated with 5-FU.The combination therapy of HQEZ with 5-FU or other chemotherapeutic drugs will also improve the anti-tumor efficacy of chemotherapy.展开更多
OBJECTIVE:To elucidate the potential molecular mechanisms of Baishao(Radix Paeoniae Alba)(APR)and Gancao(Radix Glycyrrhizae)(GR)in the treatment of major depressive disorder(MDD).METHODS:Based on the network pharmacol...OBJECTIVE:To elucidate the potential molecular mechanisms of Baishao(Radix Paeoniae Alba)(APR)and Gancao(Radix Glycyrrhizae)(GR)in the treatment of major depressive disorder(MDD).METHODS:Based on the network pharmacology strategy,the therapeutic targets of APR-GR for MDD are predicted,differentially expressed genes from the Integrated Gene Expression database for MDD patients.Topological networks are constructed,Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways are enriched,their pharmacological potential molecular mechanisms are discussed,and molecular docking analysis is performed to further motivate compositional and target interactions.Finally,the CUMS mouse model is used for validation.RESULTS:Based on the pharmacological network analysis,17 candidate genes were identified,including muscarinic acetylcholine receptor M1(CHRM1),muscarinic acetylcholine receptor M2(CHRM2),β2-adrenergic receptor(ADRB2),adrenergicα1A receptor(ADRA1A)and 5-hydroxytryptamine transfer protein(SLC6A4),etc.which are primarily involved in reactive oxygen species metabolism,neural response,oxidative stress response and other biological processes.Further analysis revealed that these targets are closely related to Ca^(2+),cyclic adenosine monophosphate,etc.,and exhibit optimal binding sites after molecular docking.Finally,in vivo experiments were performed and it was found that APR-GR significantly improved depression-like behavior and hippocampal impairment in mouse models,increasing brain levels of 5-hydroxytryptamine,dopamine and norepinephrine and decreasing serum levels of corticotropin releasing hormone,corticosterone and adreno cortico tropic hormone,while upregulating the expression of CHRM1,CHRM2 and ADRA1A in the hippocampus and downregulating the expression of SLC6A4 and ADRB2.CNCLUSION:This research sheds light on the potential molecular mechanism of APR-GR to improve MDD.展开更多
OBJECTIVE:To investigate the effect and mechanism of Sanqi(Radix Notoginseng)in treating periodontitis.METHODS:The active components and periodontitis targets were analyzed through network pharmacology and molecular d...OBJECTIVE:To investigate the effect and mechanism of Sanqi(Radix Notoginseng)in treating periodontitis.METHODS:The active components and periodontitis targets were analyzed through network pharmacology and molecular docking.A rat model of periodontitis was established and rats were treated by continuous intragastric administration of Sanqi(Radix Notoginseng)at different doses for 30 d.The alveolar bone structure was observed by micro-CT,the periodontal tissue structure was observed by hematoxylin-eosin staining,and the related proteins changes was detected by immunohistochemical staining.RESULTS:Sanqi(Radix Notoginseng)and periodontitis had a total of 96 coincident targets that were significantly enriched in the interleukin 17(IL-17),tumor necrosis factor(TNF),and advanced glycation endproducts and the receptor of advanced glycation endproducts signaling pathways.The active compound quercetin had good binding activity with interleukin 6(IL-6),vascular endothelial growth factor A(VEGFA),matrix metallopeptidase 9(MMP9),tumor necrosis factorα(TNF-α),Jun proto-oncogene(JUN),and C-X-C motif chemokine ligand 8(CXCL8)in periodontitis.Compared with normal group,the distance from the cementoenamel junction(CEJ)to the alveolar bone(AB)was increased,alveolar bone absorption was obvious,the periodontal tissue structure was disorganized,and IL-6 and TNF-αwere upregulated in periodontitis group;meanwhile,the distance from CEJ to AB was significantly decreased,alveolar bone resorption was reduced,periodontal tissue structure was improved,the expression of IL-6,TNF-α,IL-17 and retinoid-ralated orphan receptorγt(RORγt)were decreased,Forkhead Box P3(FOXP3)and IL-10 were increased after Sanqi(Radix Notoginseng)treatment.CONCLUSIONS:Sanqi(Radix Notoginseng)improves the structure of alveolar bone and gum,and reduces inflammation;the mechanism involve in inhibiting IL-17 signaling pathway to suppress Th17 and promote Treg cells differentiation.展开更多
基金National Natural Science Foundation of China Youth Found Project:Anti-Colorectal Cancer Metastasis Mechanism of Huangqi(Radix Astragali Mongolici)-Ezhu(Rhizoma Curcumae Phaeocaulis)According to the Hypoxia-Inducible Factor 2 Alpha/β-Catenin Cross-Talk Which Influence the Colon Tumor Stem Cells in Hypoxia Microenvironment(No.82003961)National Natural Science Foundation of China Youth Found Project:the Mechanism of the Compatibility of Huangqi(Radix Astragali Mongolici)and Ezhu(Rhizoma Curcumae Phaeocaulis)on the Early Metastasis of Hepatocellular Carcinoma Mediated by Cancer Associated Fibroblasts(82104408)+1 种基金Science Foundation of China Project:Involvement of Hypoxia Inducible Factor-1αSignal in Huangqi(Radix Astragali Mongolici)-Ezhu(Rhizoma Curcumae Phaeocaulis)Combination Induced Remolding of Tumor Hypoxic Microenvironment(No.82074035)Science and Technology Development Project of Traditional Chinese Medicine in Jiangsu Province:Mechanism of Huangqi(Radix Astragali Mongolici)-Ezhu(Rhizoma Curcumae Phaeocaulis)Herb Pair on the Inhibition of Colon Cancer Metastasis Through the Wnt/β-catenin Pathway(No.YB201921)。
文摘OBJECTIVE:To evaluate the effects of Huangqi(Radix Astragali Mongolici)-Ezhu(Rhizoma Curcumae Phaeocaulis)(HQEZ)on colorectal cancer therapies and to elucidate the potential mechanisms of HQEZ,especially in combination with 5-Fluorouracil(5-FU).METHODS:The anti-tumor effects of HQEZ were evaluated in colorectal cancer models both in vivo and in vitro.The network pharmacological assay was used to investigate potential mechanisms of HQEZ.Potential target genes were selected by Gene Ontology(GO)enrichment analysis,Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis,protein-protein interaction network(PPI)and molecular docking.Within key targets,potential targets related to drug sensitivity,especially the sensitivity to 5-FU,were evaluated in HCT116 in vitro by immunofluorescence,quantitative real-time polymerase chain reaction(qPCR)and Western-blot.Then,changes in potential targets were assessed in tumors from tumor-bearing mice and the expression of these targets was also evaluated in colorectal cancer(COAD)patients from the Cancer Genome Atlas Program(TCGA)database.RESULTS:HQEZ significantly enhanced the anti-tumor activity of 5-FU in vivo and inhibit the growth of HCT116 in vitro.By network pharmacological analysis,key targets,such as protein kinase B(AKT1),epidermal growth factor receptor(EGFR),adenosine triphosphate(ATP)binding cassette subfamily B member 1(ABCB1,also named multidrug resistance protein 1,MDR1),ATP binding cassette subfamily G member 2(ABCG2),thymidylate synthetase(TYMS,also named TS),prostaglandinendoperoxide synthase 2(PTGS2),matrix metallopeptidase 2(MMP2),MMP9,toll like receptor 4(TLR4),TLR9 and dihydropyrimidine dehydrogenase(DPYD),were identified.Additionally,4 potential core active ingredients(Folate,Curcumin,quercetin and kaempferol)were identified to be important for the treatment of colorectal cancer with HQEZ.In key targets,chemoresistance related targets were validated to be affected by HQEZ.Furthermore,5-FU sensitivity related targets,including MDR1,TS,EGFR,ribonucleotide reductase catalytic subunit M1,Breast and Ovarian Cancer Susceptibility Protein 1(BRCA1)and mutl homolog 1 were also significantly reduced by HQEZ both in vitro and in vivo.Finally,these validated key targets and 5-FU sensitivity related targets were demonstrated to be up-regulated in COAD patients based on TCGA database.CONCLUSION:HQEZ has synergistic effects on the antitumor activity of 5-FU in the treatment of colorectal cancer both in vivo and in vitro.The beneficial effect of HQEZ results from the inhibition of the drug sensitivity targets associated with 5-FU.The combination therapy of HQEZ with 5-FU or other chemotherapeutic drugs will also improve the anti-tumor efficacy of chemotherapy.
基金Supported by Jilin Provincial Department of Science and Technology project:Exploring the Material Basis and Action Pathways of Baihu Tang's Antipyretic Effect based on Omics Technology(20240602036RC)。
文摘OBJECTIVE:To elucidate the potential molecular mechanisms of Baishao(Radix Paeoniae Alba)(APR)and Gancao(Radix Glycyrrhizae)(GR)in the treatment of major depressive disorder(MDD).METHODS:Based on the network pharmacology strategy,the therapeutic targets of APR-GR for MDD are predicted,differentially expressed genes from the Integrated Gene Expression database for MDD patients.Topological networks are constructed,Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways are enriched,their pharmacological potential molecular mechanisms are discussed,and molecular docking analysis is performed to further motivate compositional and target interactions.Finally,the CUMS mouse model is used for validation.RESULTS:Based on the pharmacological network analysis,17 candidate genes were identified,including muscarinic acetylcholine receptor M1(CHRM1),muscarinic acetylcholine receptor M2(CHRM2),β2-adrenergic receptor(ADRB2),adrenergicα1A receptor(ADRA1A)and 5-hydroxytryptamine transfer protein(SLC6A4),etc.which are primarily involved in reactive oxygen species metabolism,neural response,oxidative stress response and other biological processes.Further analysis revealed that these targets are closely related to Ca^(2+),cyclic adenosine monophosphate,etc.,and exhibit optimal binding sites after molecular docking.Finally,in vivo experiments were performed and it was found that APR-GR significantly improved depression-like behavior and hippocampal impairment in mouse models,increasing brain levels of 5-hydroxytryptamine,dopamine and norepinephrine and decreasing serum levels of corticotropin releasing hormone,corticosterone and adreno cortico tropic hormone,while upregulating the expression of CHRM1,CHRM2 and ADRA1A in the hippocampus and downregulating the expression of SLC6A4 and ADRB2.CNCLUSION:This research sheds light on the potential molecular mechanism of APR-GR to improve MDD.
基金Scientific Research Fund of Education Department of Yunnan Province Project:Potential Targets and Molecular Mechanisms of Sanqi(Radix Notoginseng),an Active Component of Yunnan Baiyao,in the Treatment of Periodontitis(No.2022Y204)Special Project for The Selection of High-level Scientific and Technological Talents and Innovation Teams-technical Innovation Talents Training Object Project:Technical Innovation Personnel Training Object Project(202405AD350005)。
文摘OBJECTIVE:To investigate the effect and mechanism of Sanqi(Radix Notoginseng)in treating periodontitis.METHODS:The active components and periodontitis targets were analyzed through network pharmacology and molecular docking.A rat model of periodontitis was established and rats were treated by continuous intragastric administration of Sanqi(Radix Notoginseng)at different doses for 30 d.The alveolar bone structure was observed by micro-CT,the periodontal tissue structure was observed by hematoxylin-eosin staining,and the related proteins changes was detected by immunohistochemical staining.RESULTS:Sanqi(Radix Notoginseng)and periodontitis had a total of 96 coincident targets that were significantly enriched in the interleukin 17(IL-17),tumor necrosis factor(TNF),and advanced glycation endproducts and the receptor of advanced glycation endproducts signaling pathways.The active compound quercetin had good binding activity with interleukin 6(IL-6),vascular endothelial growth factor A(VEGFA),matrix metallopeptidase 9(MMP9),tumor necrosis factorα(TNF-α),Jun proto-oncogene(JUN),and C-X-C motif chemokine ligand 8(CXCL8)in periodontitis.Compared with normal group,the distance from the cementoenamel junction(CEJ)to the alveolar bone(AB)was increased,alveolar bone absorption was obvious,the periodontal tissue structure was disorganized,and IL-6 and TNF-αwere upregulated in periodontitis group;meanwhile,the distance from CEJ to AB was significantly decreased,alveolar bone resorption was reduced,periodontal tissue structure was improved,the expression of IL-6,TNF-α,IL-17 and retinoid-ralated orphan receptorγt(RORγt)were decreased,Forkhead Box P3(FOXP3)and IL-10 were increased after Sanqi(Radix Notoginseng)treatment.CONCLUSIONS:Sanqi(Radix Notoginseng)improves the structure of alveolar bone and gum,and reduces inflammation;the mechanism involve in inhibiting IL-17 signaling pathway to suppress Th17 and promote Treg cells differentiation.
