Examining the effector mechanisms of Xuebijing Injection on COVID-19 based on network pharmacology.

Abstract

Objective: To examine the potential effector mechanisms of Xuebijing (XBJ) on coronavirus disease 2019 (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. 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 “ingredient-target-pathway” effector network. 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 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.

Potential mechanism of action of Jing Fang Bai Du San in the treatment of COVID-19 using docking and network pharmacology

“…SF and XBJ inhibit inflammation and regulate immunity. XBJ also alleviated pneumonia-induced multi-organ damage [19,24]. LHQW significantly inhibited SARS-CoV-2 replication and diminished the cytokine release [13].…”

“…Many studies have reported that TCM could resist viral pneumonia by modulating cytokine production, controlling viral replication, and regulating immunological function [22]. According to the COVID-19 seventh edition diagnostic criteria, four prescriptions, QFPD, LHQW, SF, and XBJ, achieved satisfactory results [13,19,23,24]. Among them, QFPD was reported to exhibit immune regulation, anti-infection, anti-inflammation and multi-organ protection by regulating toll-like receptors, NF-κB, and MAPK signaling pathways, which subsequently inhibits the release of pro-inflammatory factors [18,23].…”

“…KEGG pathway analysis revealed that the toll-like receptors, HIF-1, PIK3K/AKT, MAPK, NF-κB, and NOD-like receptor signaling pathways had significant effects on COVID-19 therapy. The toll-like receptors and PI3K/Akt signaling pathways have already been identified as important for anti-inflammatory effects on COVID-19 [18,24]. The activation of PI3K/Akt/mTOR pathway causes pulmonary fibrosis and lung injury by increasing lung fibroblasts and lung epithelial cells [13].…”

Integrated Analysis of microRNAs and Metabolomics in Rat’s Serum Reveals Multi-action Modes of Qingfei Paidu Decoction for COVID-19 Treatment

“…Involving regulation of immunity [154], in ammatory cytokines [154][155][156][157][158][159][160] [190][191][192], virus infection [193][194][195][196][197][198][199][200][201][202][203], especially SARS-CoV-2 [196,[198][199][200][201][204][205][206], multi-organ (especially pulmonary) brosis [207][208][209][210] phospholipase C, gamma 1 (Plcg1) [219,220], in ammatory cytokines [221,222], virus infection, e.g., H1N1, HBV [223][224][225] Note: SARS-CoV-2, severe acute respiratory syndrome coronavirus-2; HTLV, human T-cell leukemia virus; HCV, hepatitis C virus; DHBV, duck hepatitis B virus; HBV, hepatitis B virus; H1N1, In uenza A virus H1N1 2009.…”

Unraveling the Molecular Mechanism of Xuebijing Injection in the Treatment of Chronic Obstructive Pulmonary Disease by Combining Network Pharmacology and Affymetrix Array

“…A real-world study noted that the incidence of adverse reactions to XBJ in clinical practice was low (0.3%) with most adverse reactions being mild. 8 Also, XBJ aids in the treatment of COPD 9 and AECOPD 10,11 due to its good effect in improving organ dysfunction and its anti-inflammatory. 12,13 and immune-modulating effects, 14,15 but its specific therapeutic mechanism is unclear.…”