PMID- 33082858 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220417 IS - 1756-0381 (Print) IS - 1756-0381 (Electronic) IS - 1756-0381 (Linking) VI - 13 DP - 2020 TI - Examining the effector mechanisms of Xuebijing injection on COVID-19 based on network pharmacology. PG - 17 LID - 10.1186/s13040-020-00227-6 [doi] LID - 17 AB - 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 kappa-light-chain-enhancer of activated B cells (NF-kappaB), 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. CI - (c) The Author(s) 2020. FAU - Zheng, Wen-Jiang AU - Zheng WJ AD - The First Clinical Medical School of Guangzhou University of Chinese Medicine, Guangzhou, China. GRID: grid.411866.c. ISNI: 0000 0000 8848 7685 FAU - Yan, Qian AU - Yan Q AD - The First Clinical Medical School of Guangzhou University of Chinese Medicine, Guangzhou, China. GRID: grid.411866.c. ISNI: 0000 0000 8848 7685 FAU - Ni, Yong-Shi AU - Ni YS AD - The Second Clinical Medical School of Guangzhou University of Chinese Medicine, Guangzhou, China. GRID: grid.411866.c. ISNI: 0000 0000 8848 7685 FAU - Zhan, Shao-Feng AU - Zhan SF AD - The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China. GRID: grid.412595.e FAU - Yang, Liu-Liu AU - Yang LL AD - The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China. GRID: grid.412595.e FAU - Zhuang, Hong-Fa AU - Zhuang HF AD - The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China. GRID: grid.412595.e FAU - Liu, Xiao-Hong AU - Liu XH AD - The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China. GRID: grid.412595.e FAU - Jiang, Yong AU - Jiang Y AUID- ORCID: 0000-0002-3609-2280 AD - Shenzhen Hospital of Integrated Traditional Chinese and Western Medicine, Shenzhen, China. LA - eng PT - Journal Article DEP - 20201016 PL - England TA - BioData Min JT - BioData mining JID - 101319161 PMC - PMC7563914 OTO - NOTNLM OT - Active ingredient OT - Coronavirus disease 2019 OT - Effector mechanism OT - Molecular docking OT - Network pharmacology OT - Xuebijing COIS- Competing interestsThe authors declare that they have no conflicts of interest. EDAT- 2020/10/22 06:00 MHDA- 2020/10/22 06:01 PMCR- 2020/10/16 CRDT- 2020/10/21 06:01 PHST- 2020/05/07 00:00 [received] PHST- 2020/10/04 00:00 [accepted] PHST- 2020/10/21 06:01 [entrez] PHST- 2020/10/22 06:00 [pubmed] PHST- 2020/10/22 06:01 [medline] PHST- 2020/10/16 00:00 [pmc-release] AID - 227 [pii] AID - 10.1186/s13040-020-00227-6 [doi] PST - epublish SO - BioData Min. 2020 Oct 16;13:17. doi: 10.1186/s13040-020-00227-6. eCollection 2020.