背景:海索巴·鲍里斯,一种经典的维吾尔族药物,用于治疗炎症性肺部疾病,如哮喘。但虎杖挥发油(HVO)在哮喘治疗中的疗效和机制尚不清楚。
目的:我们旨在表征HVO的成分,研究OVA诱导的过敏性哮喘小鼠的治疗效果,并进一步探讨其分子机制。
方法:在本研究中,我们应用二维气相色谱四极杆飞行时间质谱(GC×GC-QTOFMS)来鉴定HVO的成分。我们建立了OVA诱导的哮喘模型来研究HVO的治疗效果。为了进一步探索潜在的分子途径,我们使用网络药理学方法进行GO和KEGG途径富集,然后建立了一个成分-目标-途径网络来识别关键的分子途径。最后,使用LPS诱导的RAW264.7巨噬细胞和OVA诱导的哮喘模型来验证潜在的信号通路。
结果:GC×GC-QTOFMS分析显示存在123种HVO化合物。倍半萜和单萜是主要成分。体内研究表明,HVO抑制OVA诱导的肺组织嗜酸性粒细胞浸润,抑制IgE的升高,IL-4、IL-5和IL-13水平,下调磷酸化PI3K的表达,Akt,JNK和P38,并通过减少occludin的降解来维持上皮屏障的完整性,Zo-1、Zo-2和E-cadherin。体外研究还显示了NO释放的抑制作用和磷酸化PI3K的下调,Akt,JNK和P38水平。
结论:HVO通过抑制PI3K/Akt/JNK/P38信号通路,通过减少occludin的降解维持气道屏障的完整性,减轻OVA诱导的哮喘小鼠气道炎症。Zo-1、Zo-2和E-cadherin。
BACKGROUND: Hyssopus cuspidatus Boriss., a classic Uyghur medicine, is used to treat inflammatory lung diseases such as asthma. But the therapeutic effect and mechanism of the volatile oil of Hyssopus cuspidatus Boriss.(HVO) in asthma therapy remain unclear.
OBJECTIVE: We aim to characterize the constituents of HVO, investigate the therapeutic effect in OVA-induced allergic asthmatic mice and further explore the molecular mechanism.
METHODS: In this study, we applied two-dimensional gas chromatography quadrupole time-of-flight mass spectrometry (GC × GC-QTOF MS) to identify the ingredients of HVO. We established OVA-induced asthmatic model to investigate the therapeutic effect of HVO. To further explore the potential molecular pathways, we used network pharmacology approach to perform GO and KEGG pathways enrichment, and then built an ingredient-target-pathway network to identify key molecular pathways. Finally, LPS-induced RAW 264.7 macrophages and OVA-induced asthmatic model were used to validate the potential signaling pathways.
RESULTS: GC × GC-QTOF MS analysis revealed the presence of 123 compounds of HVO. The sesquiterpenes and monoterpenes are the main constituents. The in vivo study indicated that HVO suppressed OVA-induced eosinophilic infiltration in lung tissues, inhibited the elevation of IgE, IL-4, IL-5, and IL-13 levels, downregulated the expressions of phosphorylated PI3K, Akt, JNK and P38, and maintained epithelial barrier integrity via reducing the degradation of occludin, Zo-1, Zo-2, and E-cadherin. The in vitro study also revealed an inhibition of NO release and downregulation of phosphorylated PI3K, Akt, JNK and P38 levels.
CONCLUSIONS: HVO alleviates airway inflammation in OVA-induced asthmatic mice by inhibiting PI3K/Akt/JNK/P38 signaling pathway and maintaining airway barrier integrity via reducing the degradation of occludin, Zo-1, Zo-2, and E-cadherin.