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基于UHPLC-Q-Orbitrap HRMS技术和网络药理学探讨四子定喘颗粒治疗支气管哮喘的作用机制

Exploration of the mechanism of action of Sizi Dingchuan granules in the treatment of bronchial asthma based on UHPLC-Q-Orbitrap HRMS technology and network pharmacology

  • 摘要: 本研究采用UHPLC-Q-Orbitrap HRMS技术检测四子定喘颗粒中的中药化学成分,再利用网络药理学与分子对接技术推测四子定喘颗粒对支气管哮喘产生的影响及作用靶点和通路。UHPLC技术研究鉴定出172种化合物,包括84种黄酮类化合物、38种有机酸及其衍生物、22种苯丙素类化合物、16种有机氧化合物、3种酚类化合物、2种萜类化合物、2种糖及其糖苷类化合物、5种其他化合物,并列举出典型化合物裂解规律。利用网络药理学研究方法,最终筛选出117种化合物进行靶点预测,建立“药物-成分-靶点-病症”关系网,显示出槲皮素、五味子甲素、黄芩苷、戈米辛h、汉黄芩素等作用于支气管哮喘的靶点较多,可能是四子定喘颗粒治疗支气管哮喘的活性成分。通过蛋白质网络互作分析得到核心靶点,其中有TNF、IL6、JAK2、STAT3、BCL2、CASP3、EGFR等,主要集中在JAK-STAT信号通路上,可以推断四子定喘颗粒的主要成分可能是通过调控JAK-STAT这个信号通路来调节Th17和Treg细胞、Th1和Th2细胞之间分化的均衡,对治疗支气管哮喘起到积极作用。

     

    Abstract: This study employed ultrahigh-performance liquid chromatograph-hybrid quadrupole orbitrap high resolution mass spectrometry (UHPLC-Q-Orbitrap HRMS) to detect the chemical constituents of traditional Chinese medicine in Sizi Dingchuan granules. Network pharmacology and molecular docking techniques were then utilized to predict the effects of Sizi Dingchuan granules on bronchial asthma, along with its target molecules and signaling pathways. UHPLC analysis identified 172 compounds, including 84 flavonoids, 38 organic acids and their derivatives, 22 phenylpropanoids, 16 organic oxygen compounds, 3 phenolic compounds, 2 terpenoids, 2 sugars and glycosides, and 5 other compounds. Typical compound fragmentation patterns were documented. Using network pharmacology methods, 117 compounds were ultimately selected for target prediction, establishing a “drug-component-target-disease” network, which revealed that quercetin, schisandrin A, baicalin, gomisin H, and baicalin exhibit multiple targets related to bronchial asthma, suggesting that they may be the active components responsible for the compound’s efficacy in treating this condition. Protein-protein interaction analysis identified core targets including TNF, IL-6, JAK2, STAT3, BCL2, CASP3, and EGFR, primarily clustered within the JAK-STAT signaling pathway. This suggests that the main components of Sizi Dingchuan granules may regulate the balance between Th17 and Treg cells, as well as Th1 and Th2 cell differentiation, by modulating the JAK-STAT signaling pathway, thereby exerting a positive therapeutic effect on bronchial asthma.

     

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