Objective To investigate and predict the molecular targets and mechanism of Huanglian Jiedu Decoction(黄连解毒汤,HLJDD)in the treatment of Corona Virus Disease 2019(COV-ID-19)through network pharmacology and molecular...Objective To investigate and predict the molecular targets and mechanism of Huanglian Jiedu Decoction(黄连解毒汤,HLJDD)in the treatment of Corona Virus Disease 2019(COV-ID-19)through network pharmacology and molecular docking analysis.Methods The chemical constituents and action targets of HLJDD were retrieved on Tradi-tional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),SymMap v2,Encyclopedia of Traditional Chinese Medicine(ETCM),a High-throughput Ex-periment-and Reference-guided Database of Traditional Chinese Medicine(HERB),and Tra-ditional Chinese Medicine Integrated Database(TCMID).UniProt and GeneCards were used to query the target genes that corresponding to the active compounds,and then a compound-target network was constructed using Cytoscape 3.7.2.Gene Ontology(GO)database was used to annotate GO functions.Kyoto Encyclopedia of Genes and Genomes(KEGG)was used to predict the possible mechanisms of active compounds.The Database for Annotation,Visu-alization and Integrated Discovery(DAVID)was used to analysis the tissue enrichment.The main active compounds in HLJDD are molecularly docked with their corresponding related targets.Results Seventy-six compounds were screened and 458 corresponding targets in the network were obtained.Gene annotation showed that the targets were involved mainly in 1953 biolo-gical processes.884 signaling pathways was enriched,involving signaling by interleukins,cy-tokine signaling in immune system,generic transcription pathway,and RNA polymerase II transcription.The targets mainly distributed in the lung,liver,and placenta,involving a vari-ety of immune cells,such as T cells and B cells.The molecular docking results showed that core compounds such as wogonin,berberine,and baicalein had high affinity with tumor nec-rosis factor(TNF),insulin(INS),and tumor protein 53(TP53).Conclusion The active compounds in HLJDD may have a therapeutic effect on COVID-19 through regulating multiple signal pathways by targeting genes such as vascular endothelial growth factor A(VEGFA),INS,interleukin-6(IL-6),TNF,caspase-3,TP53,and mitogen-activ-ated protein kinase 3(MAPK3).展开更多
文摘目的研究妊娠上调的非泛素性钙调蛋白激酶(Pregnancy-upregulated nonubiquitous calmodulin kinase,PNCK)在鼻咽癌组织中的表达以及对鼻咽癌细胞增殖和凋亡的作用。方法采用免疫组织化学方法检测鼻咽癌癌组织和正常组织中PNCK表达水平。构建慢病毒载体干扰PNCK基因表达,并采用Real time PCR和免疫印迹结果证实,采用MTT方法、流式细胞术、Caspase3和Caspase7活性检测鼻咽癌肿瘤细胞增殖和凋亡的变化。结果免疫组织化学结果显示PNCK蛋白在鼻咽癌癌组织中呈特异性高表达。Real time PCR和免疫印迹结果证实慢病毒成功干扰鼻咽癌CNE-2Z细胞中PNCK表达(PNCK基因在mRNA和蛋白水平表达受到显著抑制)。MTT检测结果显示抑制PNCK表达抑制CNE-2Z细胞增殖。此外,干扰PNCK表达引起CNE-2Z细胞Caspase3和Caspase7活性上升,流式细胞术表明干扰PNCK基因表达可以促进CNE-2Z细胞凋亡。结论干扰PNCK基因表达抑制鼻咽癌细胞增殖并诱导肿瘤细胞凋亡,可能是治疗鼻咽癌的潜在靶点。
基金National Natural Science Foundation of China(81973670)Natural Science Foundation of Hunan Province(2018JJ2297)+2 种基金Key Program of Scientific Research Fund of Hunan Provincial Education Department(19A370)Domestic First-class Cultivation Discipline Integrated Traditional Chinese and Western Medicine Discipline Project of Hunan Province(2021ZXYJH10)College Student Innovation and Entrepreneurship Training Program of Hunan Province(S201910541046).
文摘Objective To investigate and predict the molecular targets and mechanism of Huanglian Jiedu Decoction(黄连解毒汤,HLJDD)in the treatment of Corona Virus Disease 2019(COV-ID-19)through network pharmacology and molecular docking analysis.Methods The chemical constituents and action targets of HLJDD were retrieved on Tradi-tional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),SymMap v2,Encyclopedia of Traditional Chinese Medicine(ETCM),a High-throughput Ex-periment-and Reference-guided Database of Traditional Chinese Medicine(HERB),and Tra-ditional Chinese Medicine Integrated Database(TCMID).UniProt and GeneCards were used to query the target genes that corresponding to the active compounds,and then a compound-target network was constructed using Cytoscape 3.7.2.Gene Ontology(GO)database was used to annotate GO functions.Kyoto Encyclopedia of Genes and Genomes(KEGG)was used to predict the possible mechanisms of active compounds.The Database for Annotation,Visu-alization and Integrated Discovery(DAVID)was used to analysis the tissue enrichment.The main active compounds in HLJDD are molecularly docked with their corresponding related targets.Results Seventy-six compounds were screened and 458 corresponding targets in the network were obtained.Gene annotation showed that the targets were involved mainly in 1953 biolo-gical processes.884 signaling pathways was enriched,involving signaling by interleukins,cy-tokine signaling in immune system,generic transcription pathway,and RNA polymerase II transcription.The targets mainly distributed in the lung,liver,and placenta,involving a vari-ety of immune cells,such as T cells and B cells.The molecular docking results showed that core compounds such as wogonin,berberine,and baicalein had high affinity with tumor nec-rosis factor(TNF),insulin(INS),and tumor protein 53(TP53).Conclusion The active compounds in HLJDD may have a therapeutic effect on COVID-19 through regulating multiple signal pathways by targeting genes such as vascular endothelial growth factor A(VEGFA),INS,interleukin-6(IL-6),TNF,caspase-3,TP53,and mitogen-activ-ated protein kinase 3(MAPK3).
