雍平风（YPF）在哮喘患者中的临床效果已经得到确认，但是缺乏一项验证其药理机制的研究。为了揭示雍平风对治疗哮喘的分子基础和潜在药理机制，本研究首先利用基于系统药理学的方法，结合药代动力学筛选、靶点预测、网络分析、GO和KEGG分析，系统地破解了雍平风在哮喘中的机制。其次，利用GEO2R在线工具鉴定了哮喘患者和健康对照组之间的差异表达基因（DEGs）。第三，在系统药理学和DEGs结果的基础上，利用Discovery Studio 2020客户端版本进行分子对接，以检测化合物和靶点之间的结合能力。最后，将卵清蛋白（OVA）挑战的C57BL/6小鼠用YPF或其有效化合物进行治疗，以评估预测效果。本研究筛选出了35个活性化合物，在靶点捕捉和匹配后确定了87个潜在的靶点进行进一步分析。芦荟素、山奈酚和黄芩素被确定为雍平风的主要成分。在KEGG富集分析中，识别出了磷脂酰肌醇3-激酶（PI3K）/蛋白激酶B（AKT）、肿瘤坏死因子（TNF）和IL-17通路作为前三名的信号通路。NCBI的GEO2R工具发现了与雍平风治疗靶点重叠的5个DEGs。通过分子对接的结果，证明黄芩素是雍平风中最活跃的化合物。体内实验表明，雍平风和黄芩素通过降低PI3K/AKT、IL-17和TNF信号通路中的炎症因子和关键因子水平，显著减轻了气道阻力和肺部炎症。YPF及其主要活性成分黄芩素可能通过多个分子靶点和信号通路包括PI3K/AKT、IL-17和TNF-α对哮喘炎症发挥治疗作用。©2023该作者。Elsevier GmbH.保留所有权利。

The clinical effect of Yupingfeng (YPF) has been confirmed in asthma patients, however, it lacks a study to verify its pharmacological mechanism.To reveal the molecular basis and potential pharmacological mechanism of YPF in the treatment of asthma.First, a systems pharmacology-based method integrating pharmacokinetic screening, target prediction, network analyses, GO and KEGG analyses were used for the systematic deciphering of the mechanism of YPF in asthma. Second, differentially expressed genes (DEGs) between asthma patients and healthy controls were identified by GEO2R online tool. Third, based on systems pharmacology and DEGs results, molecular docking was performed utilizing the Discovery Studio 2020 Client version to detect the binding capacity between compounds and targets. Finally, ovalbumin (OVA)-challenged C57BL/6 mice were treated with YPF or its effective compound to assess the predictions.A total of 35 active compounds were filtered out, with 87 potential targets being identified for further analysis after target fishing and matching. Quercetin, kaempferol, and wogonin were identified as the main ingredients in YPF. The signaling pathways of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT), tumor necrosis factor (TNF) and IL-17 were identified as the top signaling pathways in KEGG enrichment analysis. GEO2R tools of NCBI discovered five DEGs that overlapped with the therapeutic targets of YPF. Wogonin was proven to be the top active compound in YPF through the results of molecular docking. In vivo experiments indicated that YPF and wogonin significantly attenuated airway resistance and lung inflammation by decreasing the levels of inflammatory cytokines and key factors in PI3K/AKT, IL-17, and TNF signaling pathways.YPF and its main active compound wogonin may exert some therapeutic effects on asthma inflammation through multiple molecular targets and signaling pathways including PI3K/AKT, IL-17 and TNF-α.Copyright © 2023 The Author(s). Published by Elsevier GmbH.. All rights reserved.