尽管变应性鼻炎(AR)发病机制的复杂性,尚未开发出FDA批准的药物以达到最佳治疗效果。本研究通过网络药理学和实验方法探讨了黄芪(HedysarumMultijjugumMaxim)-甘草(甘草或甘草)对治疗AR的功效和机理。确定了黄芪和甘草的生物活性成分,并将其用于预测这些草药在AR中的作用靶标并生成药理网络。建立卵清蛋白(OVA)诱导的AR小鼠模型,以评估基于两种草药制备的黄芪汤(HQD)的抗AR作用。我们确定了90种黄芪-甘草对的活性成分,靶向69个AR相关基因。槲皮素(QUE)被确定为这对的中心成分,AR中有57个目标。蛋白质-蛋白质相互作用(PPI)网络分析和分子对接揭示了IL1B,TNF,STAT1,IL6,PTGS2,RELA,IL2,NFKBIA,IFNG,IL10、IL1A、IRF1,EGFR,和CXCL10作为AR治疗中QUE的重要靶点。实验上,QUE或HQD可显着减轻AR诱导的组织病理学变化,AR症状,和IgE水平和抵消AR诱导的IFNG表达变化,IRF1,RELA,NFKBIA。NF-kB抑制剂helenalin促进了这些作用,表明HQD和QUE通过在AR小鼠中通过NF-κB途径调节IFNG/IRF1信号传导来抵消小鼠的AR。这些发现揭示了黄芪-甘草对成分的功效,他们的潜在目标,以及HQD治疗AR的分子机制,这可以促进针对这种疾病的量身定制的治疗干预措施的发展。
Despite the complexity of allergic rhinitis (AR) pathogenesis, no FDA-approved drug has been developed to achieve optimal therapeutic effects. The present study explored the efficacy and mechanism of Huangqi (Hedysarum Multijugum Maxim)-Gancao (Glycyrrhizae Radix et Rhizoma or licorice) herb pair in treating AR by network pharmacology and experimental approaches. The bioactive ingredients of Huangqi and Gancao were identified and used to predict the targets of these herbs in AR and generate the pharmacological network. Ovalbumin (OVA)-induced AR mouse model was established to assess the anti-AR effect of the Huangqi decoction (HQD) prepared based on both herbs. We identified 90 active ingredients of the Huangqi-Gancao pair, targeting 69 AR-related genes. Quercetin (QUE) was identified as the hub ingredient of this pair, with 57 targets in AR. The protein-protein interaction (PPI) network analysis and molecular docking revealed IL1B, TNF, STAT1, IL6, PTGS2, RELA, IL2, NFKBIA, IFNG, IL10, IL1A, IRF1, EGFR, and CXCL10 as important targets of QUE in AR treatment. Experimentally, QUE or HQD significantly alleviated the AR-induced histopathological changes, AR symptoms, and IgE level and counteracted AR-induced expression changes of IFNG, IRF1, RELA, and NFKBIA. These effects were promoted by the NF-kB inhibitor helenalin, indicating that HQD and QUE counteracted AR in mice by regulating the IFNG/IRF1 signaling via the NF-κB pathway in AR mice. These findings shed light on the efficacy of the constituents of Huangqi-Gancao pair, their potential targets, and the molecular mechanisms of HQD in treating AR, which could advance the development of tailored therapeutic interventions for this disorder.