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. 2022 Jul 25;22(1):199.
doi: 10.1186/s12906-022-03677-z.

Network pharmacology-based analysis and experimental in vitro validation on the mechanism of Paeonia lactiflora Pall. in the treatment for type I allergy

Yang Zhao #  1 , Hui Li #  2 , Xiangsheng Li  1 , Yizhao Sun  1 , Yuxin Shao  1 , Yanfen Zhang  3 , Zhongcheng Liu  4
Affiliations

Network pharmacology-based analysis and experimental in vitro validation on the mechanism of Paeonia lactiflora Pall. in the treatment for type I allergy

Yang Zhao et al. BMC Complement Med Ther. .

Abstract

Background: The incidence of allergic reaction is increasing year by year, but the specific mechanism is still unclear. Paeonia lactiflora Pall.(PLP) is a traditional Chinese medicine with various pharmacological effects such as anti-tumor, anti-inflammatory, and immune regulation. Previous studies have shown that PLP has potential anti-allergic activity. However, there is still no comprehensive analysis of the targeted effects and exact molecular mechanisms of the anti-allergic components of PLP. This study aimed to reveal the mechanism of PLP. in the treatment of type I allergy by combining network pharmacological methods and experimental verification.

Methods: First, we used the traditional Chinese medicine systems pharmacology (TCMSP) database and analysis platform to screen the main components and targets of PLP, and then used databases such as GeneCards to retrieve target information related to 'allergy'. Protein-protein interaction (PPI) analysis obtained the core target genes in the intersection target, and then imported the intersection target into the David database for gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) analysis. Furthermore, the therapeutic effect of paeoniflorin, the main component of PLP, on IgE-induced type I allergy was evaluated in vitro.

Results: GO analysis obtained the main biological processes, cell components and molecular functions involved in the target genes. KEGG analysis screened out MAPK1, MAPK10, MAPK14 and TNF that have a strong correlation with PLP anti-type I allergy, and showed that PLP may pass through signal pathways such as IgE/FcεR I, PI3K/Akt and MAPK to regulate type I allergy. RT-qPCR and Western Blot results confirmed that paeoniflorin can inhibit the expression of key genes and down-regulate the phosphorylation level of proteins in these signal pathways. It further proved the reliability of the results of network pharmacology research.

Conclusion: The results of this study will provide a basis for revealing the multi-dimensional regulatory mechanism of PLP for the treatment of type I allergy and the development of new drugs.

Keywords: Allergic reaction; IgE/FcεR I; Traditional Chinese medicine.

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Conflict of interest statement

Not applicable.

Figures

Fig. 1
Fig. 1
Intersection of the targets of PLP and allergy
Fig. 2
Fig. 2
PPI network of PLP-allergy target
Fig. 3
Fig. 3
PPI network of top 30 target genes
Fig. 4
Fig. 4
Results of GO analysis
Fig. 5
Fig. 5
Enrichment analysis of pathways
Fig. 6
Fig. 6
Important target genes are mainly distributed in the FcεR I signal pathway
Fig. 7
Fig. 7
Network of PLP-target-pathway
Fig. 8
Fig. 8
Effect of Pae on the phosphorylation of Lyn and Syk (n = 3). a Western Blot detected the phosphorylation of Lyn and Syk in RBL-2H3 cells. b Density analysis of Lyn. c Density analysis of Syk. ##p < 0.01 vs control; **p < 0.01 vs model; ++p < 0.01 vs Keto
Fig. 9
Fig. 9
Effect of Pae on the expression of Lyn, Syk, Fyn and PLCγ in the IgE signal pathway (n = 3). a Lyn; b Syk; c Fyn; d PLCγ. ##p < 0.01 vs control; *p < 0.05, **p < 0.01 vs model; ++p < 0.01 vs Keto
Fig. 10
Fig. 10
Effect of Pae on the expression of PI3K, Akt, ERK, JNK, p38 and p65 (n = 3). (a) PI3K; (b) Akt; (c) ERK; (d) JNK; (e) p38; (f) p65.##p < 0.01 vs control; *p < 0.05, **p < 0.01 vs model; ++p < 0.01 vs Keto
Fig. 11
Fig. 11
The provable mechanism of PLP anti-Type I allergy derived from this study
Fig. 12
Fig. 12
Graphical abstract of this paper
See this image and copyright information in PMC

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