Based on IL-4/JNK/c-Jun pathway, the effect of Jianpi Yishentongqiao Keli on allergic rhinitis was studied

Abstract

objective: The objective is to investigate the mechanism of Jianpi Yishentongqiao Keli（JPYSTQKL）in the treatment of allergic rhinitis (AR) based on network pharmacology and in vivo experiments. material and Methods : The active ingredients and target of JPYSTQKL were screened by TCMSP platform, and the target of AR disease was obtained by Gene Cards, OMIM and TTD databases. Protein interaction (PPI) network was constructed with STRING platform. DAVID online database was used for GO/KEGG enrichment analysis.The construction of the JPYSTQKL active ingredient-AR disease target network was carried out using Cytoscape 3.9.1 in order to predict potential targets. The docking between key compounds and core target genes was subsequently verified using Auto-Dock Vina. Additionally, an AR rat model was established. 56 SD rats were randomly divided into Control group (group A), Model group (group B), JPYSTQKL high-dose group (group C), JPYSTQKL medium-dose group (group D), JPYSTQKL low-dose group (group E) and blocker by SPSS SP600125 group (group F) and Loratadine group (group G) were divided into groups and evaluated by behavioral, HE pathological observation, ELISA, Immuno-histo-chemistry, WB detection and other indicators. Result:196 active components, 96 targets and 157 pathways of JPYSTQKL were screened. KEGG enrichment analysis involved immuno-inflammatory signaling pathways. It is related to cell proliferation and apoptosis-related signaling pathways, such as MAPK signaling pathway and IL-17 signaling pathway. Molecular docking results showed that the active ingredient was closely bound to the target gene. In vivo experiment results showed as follows: The results of HE showed that the pathological changes of nasal mucosa in SP600125 and JPYSTQKL groups were significantly reduced, cilia were arranged in an orderly manner, the structure of nasal mucosa tended to be normal, congestion and edema were slight, and inflammatory cell infiltration was significantly improved. The ELISA findings indicated that the serum concentrations of IgE, SIgE, and IL-4 were notably increased in the Model group in comparison to the Control group (P < 0.01), whereas the level of IFN-γ showed a significant reduction. In comparison to the Model group, the intervention groups exhibited a decrease in the levels of IgE, SIgE and IL-4, while the level of IFN-γ showed an increase (P < 0.01). According to Western-blot Detection, the expression of JNK, c-JUN, P-JNK and P-C-Jun proteins in nasal mucosa of Model group was significantly up-regulated (P< 0.05).Compared with the Model group, the nasal mucosa proteins of rats treated with JNK, c-JUN, P-JNK, and P-C-Jun reduced significantly (P < 0.05 or P < 0.01). Conclusion: Jianpi Yishentongqiao Keli can a exert therapeutic effect on AR rats by inhibiting the phosphorylation of IL-4/JNK/c-Jun signaling pathway protein.