Examining the effector mechanisms of Xuebijing injection on COVID-19 based on network pharmacology
Abstract Background Chinese medicine Xuebijing (XBJ) has proven to be effective in the treatment of mild coronavirus disease 2019 (COVID-19) cases. But the bioactive compounds and potential mechanisms of XBJ for COVID-19 prevention and treatment are unclear. This study aimed to examine the potential...
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BMC
2020-10-01
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Series: | BioData Mining |
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Online Access: | http://link.springer.com/article/10.1186/s13040-020-00227-6 |
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Article |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Wen-jiang Zheng Qian Yan Yong-shi Ni Shao-feng Zhan Liu-liu Yang Hong-fa Zhuang Xiao-hong Liu Yong Jiang |
spellingShingle |
Wen-jiang Zheng Qian Yan Yong-shi Ni Shao-feng Zhan Liu-liu Yang Hong-fa Zhuang Xiao-hong Liu Yong Jiang Examining the effector mechanisms of Xuebijing injection on COVID-19 based on network pharmacology BioData Mining Active ingredient Coronavirus disease 2019 Effector mechanism Molecular docking Network pharmacology Xuebijing |
author_facet |
Wen-jiang Zheng Qian Yan Yong-shi Ni Shao-feng Zhan Liu-liu Yang Hong-fa Zhuang Xiao-hong Liu Yong Jiang |
author_sort |
Wen-jiang Zheng |
title |
Examining the effector mechanisms of Xuebijing injection on COVID-19 based on network pharmacology |
title_short |
Examining the effector mechanisms of Xuebijing injection on COVID-19 based on network pharmacology |
title_full |
Examining the effector mechanisms of Xuebijing injection on COVID-19 based on network pharmacology |
title_fullStr |
Examining the effector mechanisms of Xuebijing injection on COVID-19 based on network pharmacology |
title_full_unstemmed |
Examining the effector mechanisms of Xuebijing injection on COVID-19 based on network pharmacology |
title_sort |
examining the effector mechanisms of xuebijing injection on covid-19 based on network pharmacology |
publisher |
BMC |
series |
BioData Mining |
issn |
1756-0381 |
publishDate |
2020-10-01 |
description |
Abstract Background Chinese medicine Xuebijing (XBJ) has proven to be effective in the treatment of mild coronavirus disease 2019 (COVID-19) cases. But the bioactive compounds and potential mechanisms of XBJ for COVID-19 prevention and treatment are unclear. This study aimed to examine the potential effector mechanisms of XBJ on COVID-19 based on network pharmacology. Methods We searched Chinese and international papers to obtain the active ingredients of XBJ. Then, we compiled COVID-19 disease targets from the GeneCards gene database and via literature searches. Next, we used the SwissTargetPrediction database to predict XBJ’s effector targets and map them to the abovementioned COVID-19 disease targets in order to obtain potential therapeutic targets of XBJ. Cytoscape software version 3.7.0 was used to construct a “XBJ active-compound-potential-effector target” network and protein-protein interaction (PPI) network, and then to carry out network topology analysis of potential targets. We used the ClueGO and CluePedia plugins in Cytoscape to conduct gene ontology (GO) biological process (BP) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway enrichment analysis of XBJ’s effector targets. We used AutoDock vina and PyMOL software for molecular docking. Results We obtained 144 potential COVID-19 effector targets of XBJ. Fourteen of these targets-glyceraldehyde 3-phosphate dehydrogenase (GAPDH), albumin (ALB), tumor necrosis factor (TNF), epidermal growth factor receptor (EGFR), mitogen-activated protein kinase 1 (MAPK1), Caspase-3 (CASP3), signal transducer and activator of transcription 3 (STAT3), MAPK8, prostaglandin-endoperoxide synthase 2 (PTGS2), JUN, interleukin-2 (IL-2), estrogen receptor 1 (ESR1), and MAPK14 had degree values > 40 and therefore could be considered key targets. They participated in extracellular signal–regulated kinase 1 and 2 (ERK1, ERK2) cascade, the T-cell receptor signaling pathway, activation of MAPK activity, cellular response to lipopolysaccharide, and other inflammation- and immune-related BPs. XBJ exerted its therapeutic effects through the renin-angiotensin system (RAS), nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB), MAPK, phosphatidylinositol-4, 5-bisphosphate 3-kinase (PI3K)-protein kinase B (Akt)-vascular endothelial growth factor (VEGF), toll-like receptor (TLR), TNF, and inflammatory-mediator regulation of transient receptor potential (TRP) signaling pathways to ultimately construct a “drug-ingredient-target-pathway” effector network. The molecular docking results showed that the core 18 effective ingredients had a docking score of less than − 4.0 with those top 10 targets. Conclusion The active ingredients of XBJ regulated different genes, acted on different pathways, and synergistically produced anti-inflammatory and immune-regulatory effects, which fully demonstrated the synergistic effects of different components on multiple targets and pathways. Our study demonstrated that key ingredients and their targets have potential binding activity, the existing studies on the pharmacological mechanisms of XBJ in the treatment of sepsis and severe pneumonia, could explain the effector mechanism of XBJ in COVID-19 treatment, and those provided a preliminary examination of the potential effector mechanism in this disease. |
topic |
Active ingredient Coronavirus disease 2019 Effector mechanism Molecular docking Network pharmacology Xuebijing |
url |
http://link.springer.com/article/10.1186/s13040-020-00227-6 |
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doaj-4b180292efe24b5e9b1fdd4f440c3cd42020-11-25T03:34:50ZengBMCBioData Mining1756-03812020-10-0113112310.1186/s13040-020-00227-6Examining the effector mechanisms of Xuebijing injection on COVID-19 based on network pharmacologyWen-jiang Zheng0Qian Yan1Yong-shi Ni2Shao-feng Zhan3Liu-liu Yang4Hong-fa Zhuang5Xiao-hong Liu6Yong Jiang7The First Clinical Medical School of Guangzhou University of Chinese MedicineThe First Clinical Medical School of Guangzhou University of Chinese MedicineThe Second Clinical Medical School of Guangzhou University of Chinese MedicineThe First Affiliated Hospital of Guangzhou University of Chinese MedicineThe First Affiliated Hospital of Guangzhou University of Chinese MedicineThe First Affiliated Hospital of Guangzhou University of Chinese MedicineThe First Affiliated Hospital of Guangzhou University of Chinese MedicineShenzhen Hospital of Integrated Traditional Chinese and Western MedicineAbstract Background Chinese medicine Xuebijing (XBJ) has proven to be effective in the treatment of mild coronavirus disease 2019 (COVID-19) cases. But the bioactive compounds and potential mechanisms of XBJ for COVID-19 prevention and treatment are unclear. This study aimed to examine the potential effector mechanisms of XBJ on COVID-19 based on network pharmacology. Methods We searched Chinese and international papers to obtain the active ingredients of XBJ. Then, we compiled COVID-19 disease targets from the GeneCards gene database and via literature searches. Next, we used the SwissTargetPrediction database to predict XBJ’s effector targets and map them to the abovementioned COVID-19 disease targets in order to obtain potential therapeutic targets of XBJ. Cytoscape software version 3.7.0 was used to construct a “XBJ active-compound-potential-effector target” network and protein-protein interaction (PPI) network, and then to carry out network topology analysis of potential targets. We used the ClueGO and CluePedia plugins in Cytoscape to conduct gene ontology (GO) biological process (BP) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway enrichment analysis of XBJ’s effector targets. We used AutoDock vina and PyMOL software for molecular docking. Results We obtained 144 potential COVID-19 effector targets of XBJ. Fourteen of these targets-glyceraldehyde 3-phosphate dehydrogenase (GAPDH), albumin (ALB), tumor necrosis factor (TNF), epidermal growth factor receptor (EGFR), mitogen-activated protein kinase 1 (MAPK1), Caspase-3 (CASP3), signal transducer and activator of transcription 3 (STAT3), MAPK8, prostaglandin-endoperoxide synthase 2 (PTGS2), JUN, interleukin-2 (IL-2), estrogen receptor 1 (ESR1), and MAPK14 had degree values > 40 and therefore could be considered key targets. They participated in extracellular signal–regulated kinase 1 and 2 (ERK1, ERK2) cascade, the T-cell receptor signaling pathway, activation of MAPK activity, cellular response to lipopolysaccharide, and other inflammation- and immune-related BPs. XBJ exerted its therapeutic effects through the renin-angiotensin system (RAS), nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB), MAPK, phosphatidylinositol-4, 5-bisphosphate 3-kinase (PI3K)-protein kinase B (Akt)-vascular endothelial growth factor (VEGF), toll-like receptor (TLR), TNF, and inflammatory-mediator regulation of transient receptor potential (TRP) signaling pathways to ultimately construct a “drug-ingredient-target-pathway” effector network. The molecular docking results showed that the core 18 effective ingredients had a docking score of less than − 4.0 with those top 10 targets. Conclusion The active ingredients of XBJ regulated different genes, acted on different pathways, and synergistically produced anti-inflammatory and immune-regulatory effects, which fully demonstrated the synergistic effects of different components on multiple targets and pathways. Our study demonstrated that key ingredients and their targets have potential binding activity, the existing studies on the pharmacological mechanisms of XBJ in the treatment of sepsis and severe pneumonia, could explain the effector mechanism of XBJ in COVID-19 treatment, and those provided a preliminary examination of the potential effector mechanism in this disease.http://link.springer.com/article/10.1186/s13040-020-00227-6Active ingredientCoronavirus disease 2019Effector mechanismMolecular dockingNetwork pharmacologyXuebijing |