Tian Xi, Cui Qingfei, Wei Jinhuan, Zhang Qian, Zhang Huiyi, Yang Mengxin, Xing Yiqi, Niu Yukun, Li Wenyu, Wang Nan, Jin Yiran, Du Yingfeng
Department of Pharmaceutical Analysis, School of Pharmacy, Hebei Medical University, Shijiazhuang, Hebei, People's Republic of China.
Institute of Cash Crop, Hebei Academy of Agriculture and Forestry Sciences, Shijiazhuang, Hebei, People's Republic of China.
Drug Des Devel Ther. 2025 May 27;19:4407-4427. doi: 10.2147/DDDT.S514891. eCollection 2025.
In traditional Chinese Medicine (TCM), Zhimu ( Bunge, ZM) - Chuanbeimu ( Bulbus, CBM) (ZC) is one of the most classical herb pairs used in the treatment of lung diseases such as asthma. This study aimed to investigate how ZC affects asthma and its mechanism.
Asthma model rats were sensitized by ovalbumin. The anti-asthma efficacy of ZM, CBM and ZC were evaluated through analysis of lung function, pathological sections and biochemical indices. Metabolomics based on UHPLC-QTOF-MS was conducted to determine the synergistic anti-asthma effect of combination therapy. Asthma targets and mechanism prediction were performed using network pharmacology. Then, the potential anti-asthma mechanism of ZC was explored using RT-qPCR.
According to the lung function test, Hematoxylin-Eosin Staining experiment, ZC herb pair had an obvious anti-asthma effect over either ZM or CBM alone. It has also been demonstrated that positive effect of ZC against Th1/Th2 immune imbalance. Both metabolomics and network pharmacology were highly enriched in the arachidonic acid metabolism pathway. The mRNA expression levels of ALOX5, PLA2G4A and CYP1A2, critical targets in arachidonic acid metabolism, were significantly down-regulated by RT-qPCR.
By reducing the expression of cytokines and chemokines mediated by the arachidonic acid metabolism pathway, ZC could alleviate OVA-induced asthma in vivo. It was the first to demonstrate the complex mechanism of ZC for the treatment of asthma. Meanwhile, a new paradigm was established for evaluating the pharmacological effects of TCM drugs for asthma based on multiple mechanisms.
在传统中医（TCM）中，知母（Bunge，ZM）-川贝母（Bulbus，CBM）（ZC）是治疗哮喘等肺部疾病最经典的药对之一。本研究旨在探讨ZC对哮喘的影响及其机制。
用卵清蛋白致敏哮喘模型大鼠。通过肺功能分析、病理切片和生化指标评估ZM、CBM和ZC的抗哮喘疗效。基于超高效液相色谱-四极杆飞行时间质谱（UHPLC-QTOF-MS）的代谢组学方法用于确定联合治疗的协同抗哮喘作用。利用网络药理学进行哮喘靶点和机制预测。然后，通过逆转录定量聚合酶链反应（RT-qPCR）探索ZC潜在的抗哮喘机制。
根据肺功能测试、苏木精-伊红染色实验，药对ZC比单独使用ZM或CBM具有更明显的抗哮喘作用。还证明了ZC对Th1/Th2免疫失衡有积极作用。代谢组学和网络药理学均高度富集于花生四烯酸代谢途径。花生四烯酸代谢中的关键靶点5-脂氧合酶（ALOX5）、磷脂酶A2G4A（PLA2G4A）和细胞色素P450 1A2（CYP1A2）的mRNA表达水平通过RT-qPCR显著下调。
通过降低花生四烯酸代谢途径介导的细胞因子和趋化因子的表达，ZC可减轻体内卵清蛋白诱导的哮喘。首次阐明了ZC治疗哮喘的复杂机制。同时，建立了基于多种机制评估中药治疗哮喘药理作用的新范式。
