Molecular mechanism of Jiawei Xiaochaihu Decoction in treating cough-variant asthma based on network pharmacology and experimental validation
Objective To explore the main active ingredients and potential mechanism of action of Jiawei Xiaochaihu Decoction(JWXCHD)in treating cough-variant asthma through network pharmacology,molecular docking,and experimental validation.Methods The network pharmacology was applied to predicting the possible mechanism of action of JWXCHD in treating cough-variant asthma and molecular docking was used to predict the binding sites of active ingredients.A rat model of asthma was established,and 60 rats were randomly divided into normal group,model group,dexamethasone tablets group[0.5 mg/(kg·d)],and JWXCHD group[5 g/(kg·d)],with 15 rats in each group.The normal group and model group were given 2 mL of saline by gavage,twice a day.The serum and lung tissue of rats were collected after four weeks of administration.The levels of interleukin-6(IL-6),interleukin-13(IL-13),immunoglobulin E(IgE),and interferon-γ(INF-γ)were checked by ELISA,and the expression levels of mitogen-activated protein kinase(MAPK)and GATA-binding protein-3(GATA-3)in the lung tissue were examined by Western blot.Results Network pharmacology screened out a total of 1,483 active ingredients of JWXCHD,274 action targets,7,509 targets related to cough-variant asthma,and 204 intersection targets.GO and KEGG enrichment analyses yielded a series of biological reaction processes such as signal transduction,inflammatory response,and cell apoptosis,mainly involving the regulation of targets such as epidermal growth factor receptor(EGFR),mitogen-activated protein kinase 1(MAPK1),mitogen-activated protein kinase 3(MAPK3),RELA proto-oncogene(RELA),cellular tumor antigen P53(TP53),myelocytomatosis virus carcinoma(MYC),and protein kinase Cα(PRKCA).The results of molecular docking showed that the main active ingredients screened out had strong binding force with the targets.Compared with the normal group,IL-6,IL-13,IgE,MAPK,and GATA-3 increased(P<0.05)and INF-γ decreased(P<0.05)in the lung tissue of the model group.Compared with the model group,IL-6,IL-13,IgE,MAPK,and GATA-3 decreased(P<0.05)and INF-γ increased(P<0.05)in the lung tissue of the dexamethasone tablets group and the JWXCHD group.Compared with the dexamethasone tablets group,IL-6,IL-13,and IgE decreased and INF-γ increased in the JWXCHD group(P<0.05).Conclusion JWXCHD has therapeutic effects on cough-variant asthma,and its mechanism of action may be related to targets of EGFR,MAPK1,MAPK3,RELA,TP53,MYC,and PRKCA.
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