Effect mechanism of Ma Xing Gan Shi Decoction against influenza virus from JAK2/STAT3 signaling pathway by combining network pharmacology / 中国药理学通报

ABSTRACT

Aim To explore the effect of JAK2/STAT3 signaling pathway on lung tissue injury induced by influenza A virus in combination with network pharmacology and to further explore the intervention effect of Ma Xing Gan Shi Decoction.Methods Network pharmacological method was used to screen the signal pathway enriched by Ma Xing Gan Shi Decoction on the potential target of influenza virus.BLAB/c mice were intranasally infected with influenza A virus.The mice were divided into normal control group, model control group, oseltamivir group, antiviral granule group and Ma Xing Shigan decoction group.The animals were treated with corresponding drugs for 3 and 7 days.Body weight and lung index were detected by HE for observation of the pathological changes of lung tissues.Real-time PCR(RT-PCR)was used to detect the mRNA expression levels of JAK2, STAT3, IL-1β and IL-4 in lung tissues.Western blot and ELISA were used to detect the protein expression levels of JAK2, STAT3, IL-1β and IL-4 in lung tissues.AutoDock Vina software was used to conduct molecular docking between STAT3 and target compounds.Results The main active components of Ma Xing Gan Shi Decoction had 110 intersection targets with influenza virus and were enriched in 170 signaling pathways.Ma Xing Shigan decoction could up-regulate the body weight of mice infected with influenza A virus, improve the pathological injury of lung tissues, down-regulate the lung index and the expression levels of JAK2, STAT3, IL-1β mRNA and protein in lung tissues, and up-regulate the expression levels of IL-4 mRNA and protein.STAT3 had better binding activity with glycyrrhiza chalcone A, an active compound in Ma Xing Gan Shi Decoction.Conclusions Ma Xing Gan Shi Decoction, as an effective compound prescription of traditional Chinese medicine against influenza virus, can effectively reduce pulmonary inflammation and regulate the balance of cytokines.The possible mechanism is to alleviate the lung injury caused by influenza A virus infection in mice by inhibiting the activation of JAK2/STAT3 signal pathway.