Shenzhu Pingxiao formula treats allergic asthma through the HSP90AA1/MAPK14/PTGS2 pathway

Shenzhu Pingxiao formula is a classic Chinese medicinal prescription used for asthma. Given that its mechanism is unclear, this study aimed to evaluate anti-allergic asthma (AA) properties and predict the targets of Shenzhu Pingxiao formula. Mice were challenged using house dust mites (HDMs). The anti-AA effect of the formula was evaluated by the airway resistance and number of immune cells in bronchoalveolar lavage fluid (BALF). Network pharmacology and molecular docking were used to predict the targets. The real-time reverse-transcription PCR and western blot were applied to analyze key genes and proteins associated with IL-17 signaling pathway. Administration of formula moderated the number of immune cells and reduced the airway hyperresponsiveness. Administration of formula reduced neutrophil recruitment. HSP90AA1, PTGS2, and MAPK14 involved in IL-17 signaling pathway, were predicted to be key targets for this formula. Vina scores in molecular docking were all ≤ −9 for wogonin–HSP90AA1, wogonin–MAPK14, and wogonin–PTGS2 pairs. Shenzhu Pingxiao formula decreased the expression levels of HSP90AA1, PTGS2, and MAPK14 in HDM-challenged mouse lung. Shenzhu Pingxiao formula can reduce neutrophil recruitment and exert anti-AA effects via suppression of HSP90AA1/MAPK14/PTGS2 pathway.参术平哮方（Shenzhu Pingxiao formula）是一款用于哮喘治疗的经典中药方剂。鉴于其作用机制尚未明确，本研究旨在评估其抗过敏性哮喘（anti-allergic asthma, AA）的活性，并预测该方剂的潜在作用靶点。本研究采用屋尘螨（house dust mites, HDMs）构建小鼠过敏性哮喘模型，通过检测气道阻力及支气管肺泡灌洗液（bronchoalveolar lavage fluid, BALF）中免疫细胞计数，评估该方剂的抗AA作用效果。研究采用网络药理学与分子对接技术预测方剂的作用靶点，并通过实时逆转录聚合酶链反应（real-time reverse-transcription PCR）及蛋白质印迹（western blot）分析IL-17信号通路相关的关键基因与蛋白表达。结果显示，给药干预可调节免疫细胞数量、缓解气道高反应性，并减少中性粒细胞招募。网络药理学预测结果表明，IL-17信号通路相关的HSP90AA1、PTGS2及MAPK14为该方剂的关键作用靶点。分子对接结果显示，汉黄芩素（wogonin）与这三个靶点的结合评分（Vina score）均≤−9。在屋尘螨造模的小鼠肺组织中，参术平哮方可下调HSP90AA1、PTGS2及MAPK14的表达水平。综上，参术平哮方可通过抑制HSP90AA1/MAPK14/PTGS2通路减少中性粒细胞招募，从而发挥抗过敏性哮喘的作用。