Analysis of effect and mechanism of"San-Yang"combined treatment for influenza based on network pharmacology and animal experimentation
Objective To investigate the therapeutic effects as well as potential targets and mechanisms of Maxing Shigan decoction combined with Xiaochaihu decoction for influenza treatment based on"San-Yang"combined treatment theory.Methods The active components and targets of Maxing Shigan Decoction and Xiaochaihu Decoction were screened based on TCMSP database.The influenza-related targets were acquired through OMIM,Genecards,DisGeNET and TTD databases,and the common targets were obtained from their intersection.The common targets were imported into STRING database to construct a protein interaction network(PPI)for screening key targets.The enrichment of common targets were analyzed through DAVID database.The diagram of composition-influenza target-pathway network was constructed based on CytoScape3.9.0 platform to screen the main active components of the drugs.Sailvina was used to verify the docking between key targets and main active components.The animal model of influenza virus pneumonia was constructed to verify the protective effect of"San-Yang"combined treatment on lung index,lung pathological injury and inflammatory injury in influenza mice.Results A total of 184 active components and 316 targets in Maxing Shigan decoction and Xiaochaihu decoction,as well as 2 894 targets in influenza were found in screening,and 152 were the common targets.The key targets of PPI network screening included AKT1,STAT3 and TNF,etc.The enrichment analysis of GO and KEGG suggested that Maxing Shigan Decoction and Xiaochaihu Decoction may treat influenza by regulating IL-17,TNF,Toll-like receptor signaling pathway.Molecular docking showed that the key targets have good binding ability with the main active components.Animal experiments showed that Maxing Shigan decoction combined with Xiaochaihu decoction improved the citeria,including weight loss,lung index and reduced the inflammation,with significantly improvement of pathologic injury in lung tissues and levels of serum CCL3 and CCL5 factors.Conclusions"San-Yang"combined treatment showed good protective effect on mice with influenza viral pneumonia,and may exert anti-influenza virus effects through multi-targets and multi-pathways.