Mechanisms of the Compound of Magnoliae Flos and Xanthii Fructus Essential Oils for the Treatment of Allergic Rhinitis based on the Integration of Network Pharmacology, Molecular Docking, and Animal Experiment

Abstract

Aim and objective: Magnoliae Flos (Chinese name: Xin-Yi) and Xanthii Fructus (Chinese name: Cang-Er-Zi) are Chinese herbal medicines and have been used to treat allergic rhinitis (AR). However, the therapeutic effect, active ingredients, and probable processes of a compound of Magnoliae Flos and Xanthii Fructus in the form of essential oils (CMFXFEO) in treating AR have not been reported. This study aims to determine the efficacy of the CMFXFEO on ovalbumin (OVA)-induced AR in a rat model and to use network pharmacology and molecular docking to reveal the hub genes, biological functions, and signaling pathways of CMFXFEO against AR.

Methods: Animal experiments were applied to validate the role of CMFXFEO in the treatment of AR. 20 rats were randomly divided into four groups: control group (CON, n=5), positive control group (AR, n=5), CMFXFEO-treated group (AR+CMFXFEO, n=5), and budesonide-treated group (AR+Budesonide, n=5). Rats were stimulated with OVA to induce AR. Symptom scores assessment and histo-pathomorphological evaluation was performed. The serum level of OVA-specific immunoglobulin (Ig) E was measured. Gas Chromatograph-Mass Spectrometer analysis (GC-MS) was used to identify the monomer chemical composition of CMFXFEO. The target genes of CMFXFEO were obtained by using PubChem and SwissTargetPrediction databases. The target genes of AR were screened using GeneCards, DisGeNET, and OMIM databases. The target genes were intersected using the venny2.1 website to obtain the potential therapeutic targets of CMFXFEO for treating AR and to construct the PPI network. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were used to reveal associated signaling pathways. The Sybyl tool was used to dock the CMFXFEO with key therapeutic targets molecularly.

Results: Intranasal CMFXFEO administration significantly suppressed the allergic symptoms, reduced the inflammatory cell infiltration, and the serum level of OVA-specific immunoglobulin (Ig) E. The main components of CMFXFEO obtained through the GC-MS analysis, listed as γ-terpinene (9.4908%), limonene (7.2693%), menthol (7.1821%), β-pinene (7.1190%), β-caryophyllene (7.0396%), eucalyptol (6.1367%), linalool(5.9686%), eugenol (5.0776%). A total of 398 CMFXFEO targets and 488 AR-related targets were screened, of which 42 were common targets. The GO and KEGG pathway analyses unveiled that CMFXFEO were strongly associated with several signaling pathways, including the AGE-RAGE signaling pathway, TNF signaling pathway, and Chemokine signaling pathway. PPI network construction screened six hub genes as therapeutic targets, including STAT3, IL1B, TLR4, PTGS2, ICAM1, and VCAM1. The molecular docking verification indicated that CMFXFEO have good binding activity with therapeutic targets, and β-Pinene's docking ability with TLR4 is particularly prominent.

Conclusion: The anti-inflammatory and anti-allergic effects of CMFXFEO are to inhibit the infiltration of inflammatory cells in the OVA-induced AR rat model. The results of the network pharmacology and molecular docking deduced that the CMFXFEO may have the potential to treat AR by multiple pathways through relieving inflammatory, anti-oxidative stress response, and modulating the immune system.

Keywords: Allergic rhinitis; essential oil; magnoliae flos; molecular docking.; network pharmacology; xanthii fructus.