Network pharmacology analysis of Huangqi reveals quercetin as a therapeutic for allergic rhinitis via the RELA-regulated IFNG/IRF1 axis response

Author:

Deng Yongjun1,Shen Limin1,Zhu Huilan1,Zhou Yanying1,Hu Xin2

Affiliation:

1. Shanghai Pudong New Area Guangming Hospital of Traditional Chinese Medicine

2. Renhe Hospital in Baoshan District

Abstract

Abstract

Despite the complexity of allergic rhinitis (AR) pathogenesis, no FDA-approved drug has been developed to achieve optimal therapeutic results. Traditional Chinese Medicine (TCM) has proven advantageous in AR therapy. The present study aimed to explore the potential bioactive components of Hedysarum Multijugum Maxim (Radix Astragali or Huangqi) in the treatment of AR by network pharmacology and experimental approaches. The bioactive components of Huangqi were identified and used for predicting potential therapeutic target genes. Genes related to AR were retrieved from GeneCard and Disgenet and merged with the targets of the bioactive components of Huangqi to obtain key target genes used for generating the "bioactive compound-target gene" pharmacological network. Ovalbumin (OVA)-induced AR mouse model was established to assess the anti-AR effect of Huangqi and its hub ingredient in AR, quercetin (QUE). We identified 13 active ingredients of Huangqi that could target 67 AR pathogenesis-related genes. In addition, QUE was detected as the bioactive component targeting the highest number of AR-related genes. The protein-protein interaction (PPI) network analysis revealed that IFNG, IRF1, JUN, RELA, and NFKBIA were important targets of QUE in AR treatment. Experimentally, we demonstrated that Huangqi and QUE counteracted AR in ovalbumin (OVA)-sensitized mice by regulating the IFNG/IRF1 signaling via NF-κB pathway in AR mice. This study sheds light on efficacious constituents, potential targets, and molecular mechanisms of Huangqi in treating AR. Such knowledge is deemed crucial in advancing the development of tailored therapeutic interventions aimed at addressing AR.

Publisher

Springer Science and Business Media LLC

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