Study on the Anti-influenza Mechanism of Bingyanqing Based on Network Pharmacology and Experimental Verification
10.19378/j.issn.1003-9783.2024.07.012
- VernacularTitle:基于网络药理学和实验验证的病炎清抗流感作用机制研究
- Author:
Zikai GENG
1
;
Dajie ZHANG
;
Jiangnan ZENG
;
Siyuan KE
;
Xiaozhao BI
;
Yu LIU
Author Information
1. 滨州医学院,山东 烟台 264003
- Keywords:
Bingyanqing;
influenza;
network pharmacology;
oxidative stress;
Nrf2 signaling pathway;
mice
- From:
Traditional Chinese Drug Research & Clinical Pharmacology
2024;35(7):1035-1045
- CountryChina
- Language:Chinese
-
Abstract:
Objective This study aimed to clarify the anti-influenza virus activity of Bingyanqing(BYQ),as well as to explore the mechanism of BYQ in treating influenza through network pharmacology and experimental verification.Methods The impact of BYQ on mortality,lung index,and viral load in an influenza mouse model was detected.We collected the ingredients and targets of BYQ formula by searching databases including TCMSP,Swiss Target Prediction and consulting the literature.The"ingredients-common target"network for anti-influenza effect of BYQ was constructed using Cytoscape software.The protein-protein interaction(PPI)network was constructed using the STRING database and Cytoscape software,and the core targets were screened.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses were performed for common targets.The effect of BYQ on reducing influenza-induced oxidative damage,the expression of antioxidant and pro-oxidant enzyme,P65 phosphorylation and nuclear factor E2-related factor 2(Nrf2)nuclear translocation in vivo were investigated.Results BYQ significantly reduced mortality,lung index,pulmonary viral load and lung injury in a mouse model of influenza.We obtained one hundred and ninety-three of BYQ active compounds,which corresponded to three hundred and thirty-eight targets.There are 180 influenza-related targets among them.Nine targets,including IκBα kinase α(CHUK),IκBα kinase γ(IKBKG),NF-κB p65(RELA),tumor necrosis factor(TNF)and interleukin 6(IL6),were identified as potential core targets.GO analysis indicated that BYQ is involved in several biological functions,including antibacterial and antioxidant stress responses.KEGG analysis revealed the involvement of several viral and immune-related pathways for BYQ in treating influenza,including herpes simplex virus,influenza A virus,TNFα and toll-like receptor pathways.In vivo studies showed that high-dose BYQ significantly reduced pulmonary malondialdehyde(MDA)levels(P＜0.01)and increased total superoxide dismutase(SOD)activity(P＜0.001)in a mouse mode of influenza compared to oseltamivir phosphate.The treatment group with the combination of BYQ&oseltamivir phosphate had lower levels of NADPH oxidase 2(NOX2)and 4(NOX4)(P＜0.001),and higher levels of catalase(CAT)and glutathione peroxidase 4(GPX4)(P＜0.001)in the lungs than oseltamivir phosphate group.The combined treatment group showed more significant Nrf2 nuclear translocation(P＜0.05)than the oseltamivir phosphate group.However,there was no significant difference in P65 phosphorylation levels between the combination treatment group and the oseltamivir phosphate group(P＜0.05),but P65 phosphorylation levels in both groups were lower than in the model group(P＜0.05).Conclusion BYQ exhibits significant anti-influenza virus activity,manifests a dual effect by inhibiting the synthesis of pro-oxidant enzymes and promoting the antioxidant system,thereby alleviates the oxidative stress damage caused by influenza.
