荆芥穗挥发油（HVO）通过抑制 PI3K/Akt/JNK/P38 信号通路和维持气道屏障完整性来改善 OVA 诱导的过敏性哮喘。

The volatile oil of Hyssopus cuspidatus Boriss. (HVO) ameliorates OVA-induced allergic asthma via inhibiting PI3K/Akt/JNK/P38 signaling pathway and maintaining airway barrier integrity.

机构信息

School of Pharmacy, Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.

Department of Anatomy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.

出版信息

J Ethnopharmacol. 2024 Nov 15;334:118568. doi: 10.1016/j.jep.2024.118568. Epub 2024 Jul 11.

DOI:10.1016/j.jep.2024.118568

PMID:38996949

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

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.

AIM OF THE STUDY

We aim to characterize the constituents of HVO, investigate the therapeutic effect in OVA-induced allergic asthmatic mice and further explore the molecular mechanism.

MATERIALS AND 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.

CONCLUSION

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.

摘要

民族药理学相关性

穗薰衣草（Hyssopus cuspidatus Boriss.），一种经典的维吾尔药物，用于治疗哮喘等炎症性肺部疾病。但穗薰衣草挥发油（HVO）在哮喘治疗中的疗效和机制尚不清楚。

研究目的

本研究旨在分析 HVO 的成分，研究其在卵清蛋白（OVA）诱导的过敏性哮喘小鼠中的治疗作用，并进一步探讨其分子机制。

材料和方法

本研究采用二维气相色谱-四极杆飞行时间质谱联用（GC×GC-QTOF MS）技术鉴定 HVO 的成分。建立 OVA 诱导的哮喘模型，研究 HVO 的治疗作用。为了进一步探讨潜在的分子途径，我们采用网络药理学方法进行 GO 和 KEGG 途径富集，并构建成分-靶标-途径网络，以识别关键的分子途径。最后，利用 LPS 诱导的 RAW 264.7 巨噬细胞和 OVA 诱导的哮喘模型验证潜在的信号通路。

结果

GC×GC-QTOF MS 分析显示 HVO 中含有 123 种化合物。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、IL-4、IL-5 和 IL-13 水平升高，下调磷酸化 PI3K、Akt、JNK 和 P38 的表达，并通过减少 occludin、Zo-1、Zo-2 和 E-cadherin 的降解来维持上皮屏障完整性。体外研究也显示其抑制一氧化氮（NO）释放和下调磷酸化 PI3K、Akt、JNK 和 P38 水平。