VEGF 和 EGFR 信号通路参与了黄芩素抑制卵清蛋白诱导的小鼠气道炎症和气道重塑。

BACKGROUND: Although Traditional Chinese Medicine (TCM) has been used for treating asthma for centuries, the understanding of its mechanism of action is still limited. Thus, the purpose of this study was to explore the possible therapeutic effects, and underlying mechanism of baicalein in the treatment of asthma. METHODS: Freely availabled atabases (e.g. OMIM, TTD, Genecards, BATMAN-TCM, STITCH 5.0, SEA, SwissTargetPrediction) and software (e.g. Ligplot 2.2.5 and PyMoL) were used for disease drug target prediction and molecular docking by network pharmacology. The efficacy and mechanism of action of baicalein in the treatment of asthma were validated using an ovalbumin (OVA)-induced asthma mouse model and molecular biology techniques. RESULTS: A total of 1655 asthma-related genes and 161 baicalein-related targets were identified from public databases. Utilizing common databases and software for network pharmacology and molecular docking analysis, seven potential target proteins for the therapeutic effects of baicalein on asthma were selected, including v-akt murine thymoma viral oncogene homolog 1 (AKT1), vascular endothelial growth factor A (VEGFA), epidermal growth factor receptor (EGFR), proto-oncogene tyrosine-protein kinase Src (SRC), mitogen-activated protein kinase 3 (MAPK3), matrix metallopeptidase 9 (MMP9), and MAPK1. In vivo, baicalein treatment via intraperitoneal injection at a dose of 50 mg/kg significantly reduced airway inflammation, collagen deposition, smooth muscle thickness, lung interleukin (IL)-4 and IL-13 levels, peripheral blood immunoglobulin (Ig)E levels, as well as the count and ratio of eosinophils in bronchoalveolar lavage fluid (BALF) in an OVA-induced asthma mouse model. Further validation by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blotting analysis revealed that the VEGF and EGFR signaling pathways involving VEGFA, MAPK1, MAPK3, and EGFR were inhibited by baicalein in the asthma mouse model. CONCLUSION: Baicalein attenuates airway inflammation and airway remodeling through inhibition of VEGF and EGFR signaling pathways in an OVA-induced asthma mouse model. This will provide a new basis for the development of baicalein as a treatment for asthma and highlights the potential of network pharmacology and molecular docking in drug discovery and development.

背景：尽管中医药（TCM）在治疗哮喘方面已经有几个世纪的历史，但对其作用机制的理解仍然有限。因此，本研究旨在探讨白杨素治疗哮喘的可能疗效及其潜在机制。

方法：利用网络药理学的方法，从公开数据库（如 OMIM、TTD、Genecards、BATMAN-TCM、STITCH 5.0、SEA、SwissTargetPrediction）和软件（如 Ligplot 2.2.5 和 PyMOL）中预测疾病药物靶点，并进行分子对接。利用卵清蛋白（OVA）诱导的哮喘小鼠模型和分子生物学技术，验证白杨素治疗哮喘的疗效和作用机制。

结果：从公共数据库中总共鉴定出 1655 个哮喘相关基因和 161 个白杨素相关靶点。利用网络药理学和分子对接分析的常见数据库和软件，选择了白杨素治疗哮喘的七个潜在作用靶点蛋白，包括 v-akt 鼠胸腺瘤病毒癌基因同源物 1（AKT1）、血管内皮生长因子 A（VEGFA）、表皮生长因子受体（EGFR）、原癌基因酪氨酸蛋白激酶Src（SRC）、丝裂原活化蛋白激酶 3（MAPK3）、基质金属蛋白酶 9（MMP9）和 MAPK1。在体内，腹腔注射 50mg/kg 白杨素可显著减轻气道炎症、胶原沉积、平滑肌厚度、肺白细胞介素（IL）-4 和 IL-13 水平、外周血免疫球蛋白（Ig）E 水平以及支气管肺泡灌洗液（BALF）中嗜酸性粒细胞的计数和比例在 OVA 诱导的哮喘小鼠模型中。通过逆转录定量聚合酶链反应（RT-qPCR）和蛋白质印迹分析进一步验证，发现白杨素抑制哮喘小鼠模型中的 VEGF 和 EGFR 信号通路，涉及 VEGFA、MAPK1、MAPK3 和 EGFR。

结论：白杨素通过抑制 OVA 诱导的哮喘小鼠模型中的 VEGF 和 EGFR 信号通路，减轻气道炎症和气道重塑。这为将白杨素开发为治疗哮喘的药物提供了新的依据，并凸显了网络药理学和分子对接在药物发现和开发中的潜力。