硬尖神香草抗支气管哮喘气道重塑的质量标志物研究
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| 篇名: | 硬尖神香草抗支气管哮喘气道重塑的质量标志物研究 |
| TITLE: | Study on quality markers of Hyssopus cuspidatus against airway remodeling in bronchial asthma |
| 摘要: | 目的 挖掘硬尖神香草抗支气管哮喘(简称“哮喘”)气道重塑的质量标志物(Q-Marker),为基于药效活性的硬尖神香草质量控制研究提供参考。方法通过网络药理学方法筛选出硬尖神香草的潜在活性成分及作用靶点;以人气道平滑肌细胞(HASMCs)为对象,以血小板衍化生长因子BB(PDGF-BB)诱导构建气道重塑细胞模型,对硬尖神香草及潜在活性成分的抗哮喘作用进行验证;采用高效液相色谱法,建立14批硬尖神香草样品的指纹图谱并进行化学计量学分析;综合药效学实验和指纹图谱结果,确定硬尖神香草抗哮喘气道重塑的Q-Marker。结果与结论网络药理学分析结果显示,硬尖神香草抗哮喘的潜在活性成分包括木犀草素、槲皮素、迷迭香酸等黄酮类和酚酸类化合物,抗哮喘的核心靶点为白细胞介素6、丝裂原活化蛋白激酶等。体外实验结果证实,25、50、100μg/mL硬尖神香草及新绿原酸(80μmol/L)、金合欢素(80μmol/L)、丹酚酸B(40μmol/L)、槲皮素-3-O-β-D-吡喃葡萄糖苷酸(80μmol/L)均可显著降低PDGF-BB诱导的细胞存活率,抑制细胞增殖、迁移和细胞外信号调控蛋白激酶1/2的磷酸化,降低白细胞介素6、肿瘤坏死因子α、活性氧水平,使细胞普遍阻滞于G0/G1期(P<0.05)。指纹图谱分析结果显示,14批硬尖神香草样品的指纹图谱共有27个共有峰,指认出新绿原酸等15个化合物,指纹图谱相似度均大于0.8;14批样品可分为3类,S1~S7为一类,S8~S13为一类,S14为一类;迷迭香酸、绿原酸、咖啡酸、三裂鼠尾草素、木犀草素、阿魏酸、槲皮素-3-O-β-D-吡喃葡萄糖苷酸及峰5、8对应成分的变量重要性投影大于1,为影响药材质量的潜在差异性标志物。综合网络药理学、体外实验验证、化学计量学分析可知,迷迭香酸、新绿原酸、咖啡酸、三裂鼠尾草素、木犀草素、阿魏酸、槲皮素-3-O-β-D-吡喃葡萄糖苷酸、金合欢素、丹酚酸B、绿原酸可能是硬尖神香草抗哮喘气道重塑的Q-Marker。 |
| ABSTRACT: | OBJECTIVE To identify the quality markers (Q-Markers) of Hyssopus cuspidatus against airway remodeling in bronchial asthma (referred to as “asthma”), an d to provide a reference for the quality control research of H. cuspidatus based on pharmacodynamic activity. METHODS Potential active components and action targets of H. cuspidatus were screened by network pharmacology method. Using human airway smooth muscle cells (HASMCs) as objects, airway remodeling cell model was induced by platelet-derived growth factor-BB (PDGF-BB); validation test was then performed for anti-asthmatic effects of H. cuspidatus and the potential active components. HPLC method was employed to establish the fingerprints of 14 batches of H. cuspidatus samples, and chemometric analysis was also conducted. Combined with the results of pharmacodynamic experiments and fingerprint analysis, the Q-Markers of H. cuspidatus against airway remodeling in asthma were determined. RESULTS&CONCLUSIONS Network pharmacology analysis showed that the potential active components of H. cuspidatus against asthma might be flavonoids and phenolic acids such as luteolin, quercetin and rosmarinic acid, and the core anti-asthmatic targets were interleukin-6, mitogen-activated protein kinase, etc. In vitro experimental results confirmed that 25, 50, 100 μg/mL of H. cuspidatus , as well as neochlorogenic acid (80 μmol/L), acacetin (80 μmol/L), salvianolic acid B (40 μmol/L) and quercetin-3- O - β -D-glucuronide (80 μmol/L), significantly reduced the cell viability induced by PDGF-BB, inhibited cell proliferation, migration, and the phosphorylation level of extracellular signal-regulated protein kinase 1/2, decreased the levels of interleukin-6, tumor necrosis factor-α and reactive oxygen species, and generally arrested cells in the G 0 /G 1 phase ( P <0.05). Fingerprint analysis showed that there were 27 common peaks in the fingerprints of the 14 batches of H. cuspidatus samples, with 15 compounds (including luteolin) identified, and the similarities of fingerprints were all greater than 0.8. The 14 batches of samples could be divided into three categories: S1-S7 as one category, S8-S13 as one category, and S14 as one category. The variable importance in the projection values of rosmarinic acid, chlorogenic acid, caffeic acid, salvigenin, luteolin, ferulic acid, quercetin-3- O - β -D-glucuronide, and the components corresponding to peaks 5 and 8 were greater than 1, indicating they were potential differential markers affecting quality. Integrating network pharmacology, in vitro experimental validation, and chemometric analysis, rosmarinic acid, neochlorogenic acid, caffeic acid, salvigenin, luteolin, ferulic acid, quercetin-3- O - β -D-glucuronide, acacetin, salvianolic acid B and chlorogenic acid may be the Q-Markers of H. cuspidatus against asthma. |
| 期刊: | 2026年第37卷第06期 |
| 作者: | 蔡晓翠;郭君婷;赵婷婷;刘桂花 |
| AUTHORS: | CAI Xiaocui,GUO Junting,ZHAO Tingting,LIU Guihua |
| 关键字: | 硬尖神香草;质量标志物;支气管哮喘;气道重塑;网络药理学;指纹图谱 |
| KEYWORDS: | Hyssopus cuspidatus; quality markers; bronchial asthma; airway remodeling; network pharmacology; fingerprint |
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