Uncovering the pharmacological mechanisms of Xijiao Dihuang decoction combined with Yinqiao powder in treating influenza viral pneumonia by an integrative pharmacology strategy

Xijiao Dihuang decoction combined with Yinqiao powder (XDD-YQP) is a classical combination formula; however, its therapeutic effects in treating influenza viral pneumonia and the pharmacological mechanisms remain unclear. The therapeutic effect of XDD-YQP in influenza viral pneumonia was evaluated in mice. Subsequently, an everted gut sac model coupled with UPLC/Q-TOF MS were used to screen and identify the active compounds of XDD-YQP. Furthermore, network pharmacological analysis was adopted to probe the mechanisms of the active compounds. Lastly, we verified the targets predicted from network pharmacological analysis by differential bioinformatics analysis. Animal experiments showed that XDD-YQP has a therapeutic effect on influenza viral pneumonia. Moreover, 113 active compounds were identified from intestinal absorbed solutions of XDD-YQP. Using network pharmacological analysis, 90 major targets were selected as critical in the treatment of influenza viral pneumonia through 12 relevant pathways. Importantly, the MAPK signaling pathway was found to be closely associated with the other 11 pathways. Moreover, seven key targets, EGFR, FOS, MAPK1, MAP2K1, HRAS, NRAS, and RELA, which are common targets in the MAPK signaling pathway, were investigated. These seven key targets were identified as differentially expressed genes (DEGs) between influenza virus-infected and uninfected individuals. Hence, the seven key targets in the MAPK signaling pathway may play a vital role in the treatment of influenza viral pneumonia with XDD-YQP. This research may offer an integrative pharmacology strategy to clarify the pharmacological mechanisms of traditional Chinese medicines. The results provide a theoretical basis for a broader clinical application of XDD-YQP.