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LitCovid-PD-FMA-UBERON

LitCovid-PD-UBERON

{"project":"LitCovid-PD-UBERON","denotations":[{"id":"T13","span":{"begin":421,"end":444},"obj":"Body_part"},{"id":"T14","span":{"begin":427,"end":444},"obj":"Body_part"},{"id":"T15","span":{"begin":481,"end":487},"obj":"Body_part"},{"id":"T16","span":{"begin":3605,"end":3609},"obj":"Body_part"},{"id":"T17","span":{"begin":3667,"end":3671},"obj":"Body_part"},{"id":"T18","span":{"begin":4089,"end":4093},"obj":"Body_part"}],"attributes":[{"id":"A13","pred":"uberon_id","subj":"T13","obj":"http://purl.obolibrary.org/obo/UBERON_0001557"},{"id":"A14","pred":"uberon_id","subj":"T14","obj":"http://purl.obolibrary.org/obo/UBERON_0000065"},{"id":"A15","pred":"uberon_id","subj":"T15","obj":"http://purl.obolibrary.org/obo/UBERON_0000341"},{"id":"A16","pred":"uberon_id","subj":"T16","obj":"http://purl.obolibrary.org/obo/UBERON_0002048"},{"id":"A17","pred":"uberon_id","subj":"T17","obj":"http://purl.obolibrary.org/obo/UBERON_0002048"},{"id":"A18","pred":"uberon_id","subj":"T18","obj":"http://purl.obolibrary.org/obo/UBERON_0002048"}],"text":"Discussion\nThe theory of TCM has been formed and developed for thousands of years in China. In China, TCM has a good therapeutic effect on COVID-19, which has been written into the diagnosis and treatment guidelines. The guideline points out that the combination of traditional Chinese and western medicine should be strengthened in the treatment process 34. SFJDC is a traditional Chinese medicine, mainly used to treat upper respiratory tract infections, such as influenza, sore throat, mumps, streptococcus, etc. 21. Now, SFJDC has become an effective drug for the treatment of COVID-19 35. In recent years, the research on Chinese medicine prescriptions has developed to the level of effective parts, components, components. Network pharmacology can better understand and demonstrate the interaction between multi-component multi-target and disease 36. This study aims to analyze the active components and potential mechanism of SFJDC in the treatment of COVID-19 through network pharmacology.\nIn the present study, the ingredients-targets network of SFJDC was constructed using 110 ingredients and 120 targets. The network contained 117 nodes and 419 edges which indicated the compound-target genes interaction. The results showed that most compounds of SFJDC were affected by multiple target genes, such as Wogonin, licochalcone a and acacetin acted on 42, 30 and 23 target genes, respectively. Various compounds of SFJDC may have the same targets to achieve synergy. Wogonin, a naturally occurring flavonoid, has been shown to multi-activity, such as anti-inflammatory, anti-fibrosis, anti-cancer and chondroprotective properties 37. Study showed that wogonin had an anti-infulenza activity by modulation of AMPK pathway 38. Licochalcone a, a flavonoid extracted from licorice toot, was known for its anti-inflammatory, anti-cancer, anti-oxidative and anti-bacterial bioactivity 39. Acacetin, a flavone compound, played an important role in anti-inflammatory and anti-peroxidative 40.\nIn addition, they have high OB and acacetin from 2 herbs (PR, IR) of SFJDC. The three main ingredients were anti-inflammatory and COVID-19 caused by a series of inflammatory storms. Hence, they might be the crucial effective compounds of SFJDC according the network.\nPPI network of SFJDC against NCP were visualized using Cytoscape software to obtain the candidate target genes. In order to obtain the more accurate genes, two parameters including DC and BC were used to screen nodes and structure a new network. 169 genes were eventually identified for SFJDC against NCP including 156 other human genes and 13 target genes.\nTwenty-three candidate genes (CGs) were identified by using the VennDiagram package. CGs were enriched in BP, CC, MF by GO enrichment analysis. Based on GO terms data, we found that some terms were response to lipopolysaccharide or bacterial origin, membrane raft, membrane microdomain, BH domain binding and cytokine receptor binding. COVID-19 infections leaded to a strong immune response and inflammatory storm in which a large number of cytokines were activated, so SFJDC might regulate COVID-19 through the above biological processes.\nSFJDC, as a TCM formula, has multi-component, multi-target-gene, multi-pathway. In the present study, 110 KEGG pathways were significantly enriched. Seven of the top 20 pathways were associated with viral infection including Kaposi sarcoma-associated herpesvirus infection, Human cytomegalovirus infection, Hepatitis B, Influenza A, Epstein-Barr virus infection, Human immunodeficiency virus 1 infection and Measles, and three were associated with lung disease contained tuberculosis, pertussis and small cell lung cancer. Multiple targets of SFJDC may also inhibit the activation of cytokines and reduce inflammation by regulating cytokine pathways, such as IL-17 signaling pathway and TNF signaling pathway. In this study, we obtained 20 functional annotation clusters through DAVID. Annotation Cluster1 including Asthma, Bronchiolitis Viral, Respiratory Syncytial Virus Infections, respiratory syncytial virus bronchiolitis were lung related diseases and Virus infection disease.\nGene-pathway network was constructed to the core and key target genes. The network showed that RELA had largest degree, was the core target gene. Other top five genes such as MAPK1, MAPK14, CASP3, CASP8 and IL6 might be the key target genes. The pathophysiological process of Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-COV-2) infection is similar to that of SARS-CoV infection, with a strong inflammatory response. The SARS-COV-2 virus mainly targets respiratory epithelial cells, alveolar epithelial cells, vascular endothelial cells and pulmonary macrophages, all of which express Angiotensin converting enzyme 2 (ACE2) receptor, triggering the generation of pro- inflammatory cytokines and chemokines (including IL-6, TNF, IL-10 and MCP1) 41. The NF-kB family member RELA is a widely expressed and effective transcriptional activator that activates the expression of many inflammatory through exposure to pathogens and inflammatory cytokines 42. RELA may play an important role in the infection of COVID-19. MAPK1 and MAPK14 are members of the MAPK family, which can regulate multiple cellular processes, such as response to oxidative stress, anti-inflammatory, immune response, apoptosis and cell proliferation 43. Joseph et al showed SASR-CoV-2 could induce severe inflammation by directly activating p38 MAPK pathway and many p38 MAPK inhibitors are in the clinical stage and should be considered for clinical trial for severe COVID-19 infection 44. CASP3 and CASP8, a family of cysteine-dependent proteases, play an important role in these events through activation of other apoptotic proteins mediated by proteolysis and cleavage of nuclear proteins 45. In Krahling's study, infection of 293/ACE2 cells with SARS-CoV activated apoptosis-associated events, such as caspase3, caspase 846. Therefore, we conclude that CASP3 and CASP8 may be activated and play an important role in the pathophysiological process of COVID-19. Higher plasma level of IL-6 was found in ICU patients with COVID-1947. Tocilizumab, a recombinant humanized anti-human IL-6 receptor monoclonal antibody, improved the clinical outcome in 20 severe and critical COVID-19 patients and is an effective treatment to reduce mortality 48.\nIt has been clinically confirmed that SFJDC is effective in the treatment of COVID-19. Wang et al shown that conventional treatment combined with SFJDC treatment for 4 cases of COVID-19 patients could significantly improve symptoms and promote viral negative conversion 49. Another study including 70 COVID-19 patients found that SFJDC combined with Arbidol for COVID-19 compared with single using Arbidol could significantly shorten the time of clinical symptoms improvement and COVID-19 negative conversion 50.\nTo summarise, the compound and targets of SFJDC were systematically studied by applying network pharmacology. Wogonin, licochalcone a and acacetin regulated the most targets associated with NCP. RELA, MAPK1, MAPK14, CASP3, CASP8 and IL6 were the core and key genes in the gene-network of SFJDC for the treatment of NCP. SFJDC regulated novel coronavirus pneumonia by multi-compound and multi-target, which provided theoretical support for SFJDC against COVID-19. More mechanism and roles require further clinical validation."}

LitCovid-PD-MONDO

LitCovid-PD-CLO

LitCovid-PD-CHEBI

LitCovid-PubTator

LitCovid-PD-HP

LitCovid-PD-GO-BP

LitCovid-sentences

2_test

{"project":"2_test","denotations":[{"id":"33029094-23787177-50187134","span":{"begin":853,"end":855},"obj":"23787177"},{"id":"33029094-28237856-50187135","span":{"begin":1637,"end":1639},"obj":"28237856"},{"id":"33029094-29521106-50187136","span":{"begin":1728,"end":1730},"obj":"29521106"},{"id":"33029094-22400806-50187137","span":{"begin":1886,"end":1888},"obj":"22400806"},{"id":"33029094-29243040-50187138","span":{"begin":1988,"end":1990},"obj":"29243040"},{"id":"33029094-32346093-50187139","span":{"begin":4893,"end":4895},"obj":"32346093"},{"id":"33029094-32101750-50187140","span":{"begin":5096,"end":5098},"obj":"32101750"},{"id":"33029094-28550733-50187141","span":{"begin":5366,"end":5368},"obj":"28550733"},{"id":"33029094-32422320-50187142","span":{"begin":5603,"end":5605},"obj":"32422320"},{"id":"33029094-19109397-50187143","span":{"begin":5941,"end":5944},"obj":"19109397"},{"id":"33029094-32350134-50187144","span":{"begin":6359,"end":6361},"obj":"32350134"},{"id":"T10094","span":{"begin":853,"end":855},"obj":"23787177"},{"id":"T33835","span":{"begin":1637,"end":1639},"obj":"28237856"},{"id":"T23665","span":{"begin":1728,"end":1730},"obj":"29521106"},{"id":"T6828","span":{"begin":1886,"end":1888},"obj":"22400806"},{"id":"T7761","span":{"begin":1988,"end":1990},"obj":"29243040"},{"id":"T53886","span":{"begin":4893,"end":4895},"obj":"32346093"},{"id":"T53825","span":{"begin":5096,"end":5098},"obj":"32101750"},{"id":"T29108","span":{"begin":5366,"end":5368},"obj":"28550733"},{"id":"T27530","span":{"begin":5603,"end":5605},"obj":"32422320"},{"id":"T42089","span":{"begin":5941,"end":5944},"obj":"19109397"},{"id":"T80753","span":{"begin":6359,"end":6361},"obj":"32350134"}],"text":"Discussion\nThe theory of TCM has been formed and developed for thousands of years in China. In China, TCM has a good therapeutic effect on COVID-19, which has been written into the diagnosis and treatment guidelines. The guideline points out that the combination of traditional Chinese and western medicine should be strengthened in the treatment process 34. SFJDC is a traditional Chinese medicine, mainly used to treat upper respiratory tract infections, such as influenza, sore throat, mumps, streptococcus, etc. 21. Now, SFJDC has become an effective drug for the treatment of COVID-19 35. In recent years, the research on Chinese medicine prescriptions has developed to the level of effective parts, components, components. Network pharmacology can better understand and demonstrate the interaction between multi-component multi-target and disease 36. This study aims to analyze the active components and potential mechanism of SFJDC in the treatment of COVID-19 through network pharmacology.\nIn the present study, the ingredients-targets network of SFJDC was constructed using 110 ingredients and 120 targets. The network contained 117 nodes and 419 edges which indicated the compound-target genes interaction. The results showed that most compounds of SFJDC were affected by multiple target genes, such as Wogonin, licochalcone a and acacetin acted on 42, 30 and 23 target genes, respectively. Various compounds of SFJDC may have the same targets to achieve synergy. Wogonin, a naturally occurring flavonoid, has been shown to multi-activity, such as anti-inflammatory, anti-fibrosis, anti-cancer and chondroprotective properties 37. Study showed that wogonin had an anti-infulenza activity by modulation of AMPK pathway 38. Licochalcone a, a flavonoid extracted from licorice toot, was known for its anti-inflammatory, anti-cancer, anti-oxidative and anti-bacterial bioactivity 39. Acacetin, a flavone compound, played an important role in anti-inflammatory and anti-peroxidative 40.\nIn addition, they have high OB and acacetin from 2 herbs (PR, IR) of SFJDC. The three main ingredients were anti-inflammatory and COVID-19 caused by a series of inflammatory storms. Hence, they might be the crucial effective compounds of SFJDC according the network.\nPPI network of SFJDC against NCP were visualized using Cytoscape software to obtain the candidate target genes. In order to obtain the more accurate genes, two parameters including DC and BC were used to screen nodes and structure a new network. 169 genes were eventually identified for SFJDC against NCP including 156 other human genes and 13 target genes.\nTwenty-three candidate genes (CGs) were identified by using the VennDiagram package. CGs were enriched in BP, CC, MF by GO enrichment analysis. Based on GO terms data, we found that some terms were response to lipopolysaccharide or bacterial origin, membrane raft, membrane microdomain, BH domain binding and cytokine receptor binding. COVID-19 infections leaded to a strong immune response and inflammatory storm in which a large number of cytokines were activated, so SFJDC might regulate COVID-19 through the above biological processes.\nSFJDC, as a TCM formula, has multi-component, multi-target-gene, multi-pathway. In the present study, 110 KEGG pathways were significantly enriched. Seven of the top 20 pathways were associated with viral infection including Kaposi sarcoma-associated herpesvirus infection, Human cytomegalovirus infection, Hepatitis B, Influenza A, Epstein-Barr virus infection, Human immunodeficiency virus 1 infection and Measles, and three were associated with lung disease contained tuberculosis, pertussis and small cell lung cancer. Multiple targets of SFJDC may also inhibit the activation of cytokines and reduce inflammation by regulating cytokine pathways, such as IL-17 signaling pathway and TNF signaling pathway. In this study, we obtained 20 functional annotation clusters through DAVID. Annotation Cluster1 including Asthma, Bronchiolitis Viral, Respiratory Syncytial Virus Infections, respiratory syncytial virus bronchiolitis were lung related diseases and Virus infection disease.\nGene-pathway network was constructed to the core and key target genes. The network showed that RELA had largest degree, was the core target gene. Other top five genes such as MAPK1, MAPK14, CASP3, CASP8 and IL6 might be the key target genes. The pathophysiological process of Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-COV-2) infection is similar to that of SARS-CoV infection, with a strong inflammatory response. The SARS-COV-2 virus mainly targets respiratory epithelial cells, alveolar epithelial cells, vascular endothelial cells and pulmonary macrophages, all of which express Angiotensin converting enzyme 2 (ACE2) receptor, triggering the generation of pro- inflammatory cytokines and chemokines (including IL-6, TNF, IL-10 and MCP1) 41. The NF-kB family member RELA is a widely expressed and effective transcriptional activator that activates the expression of many inflammatory through exposure to pathogens and inflammatory cytokines 42. RELA may play an important role in the infection of COVID-19. MAPK1 and MAPK14 are members of the MAPK family, which can regulate multiple cellular processes, such as response to oxidative stress, anti-inflammatory, immune response, apoptosis and cell proliferation 43. Joseph et al showed SASR-CoV-2 could induce severe inflammation by directly activating p38 MAPK pathway and many p38 MAPK inhibitors are in the clinical stage and should be considered for clinical trial for severe COVID-19 infection 44. CASP3 and CASP8, a family of cysteine-dependent proteases, play an important role in these events through activation of other apoptotic proteins mediated by proteolysis and cleavage of nuclear proteins 45. In Krahling's study, infection of 293/ACE2 cells with SARS-CoV activated apoptosis-associated events, such as caspase3, caspase 846. Therefore, we conclude that CASP3 and CASP8 may be activated and play an important role in the pathophysiological process of COVID-19. Higher plasma level of IL-6 was found in ICU patients with COVID-1947. Tocilizumab, a recombinant humanized anti-human IL-6 receptor monoclonal antibody, improved the clinical outcome in 20 severe and critical COVID-19 patients and is an effective treatment to reduce mortality 48.\nIt has been clinically confirmed that SFJDC is effective in the treatment of COVID-19. Wang et al shown that conventional treatment combined with SFJDC treatment for 4 cases of COVID-19 patients could significantly improve symptoms and promote viral negative conversion 49. Another study including 70 COVID-19 patients found that SFJDC combined with Arbidol for COVID-19 compared with single using Arbidol could significantly shorten the time of clinical symptoms improvement and COVID-19 negative conversion 50.\nTo summarise, the compound and targets of SFJDC were systematically studied by applying network pharmacology. Wogonin, licochalcone a and acacetin regulated the most targets associated with NCP. RELA, MAPK1, MAPK14, CASP3, CASP8 and IL6 were the core and key genes in the gene-network of SFJDC for the treatment of NCP. SFJDC regulated novel coronavirus pneumonia by multi-compound and multi-target, which provided theoretical support for SFJDC against COVID-19. More mechanism and roles require further clinical validation."}

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PMC:7532482 / 17209-24609 JSON TXT