IF 5.3 3区 医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE
Xu Wang, Hui-Ming Peng, Meng-Ru Zhang, Jing-Jing Li, Chuan-Peng Zhao, Ya-Li Zhang, Si-Yu Wang, Si-Ying Zhu, Jian-Kang Lu, Hai-Long Yin, Qiang Yin, Jin-Bo Fang
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引用次数: 0

摘要

背景:类固醇耐药哮喘(SRA)是一种对皮质类固醇治疗耐药的哮喘,其特征是中性粒细胞为主的炎症反应和中性粒细胞胞外陷阱(NET)的形成。Hyssopus cuspidatus Boriss.是一种维吾尔族传统药物,因其在治疗哮喘等肺部炎症方面的疗效而闻名。然而,Hyssopus cuspidatus Boriss.的挥发油(HVO)对 SRA 的治疗效果和潜在机制尚未完全阐明:本研究建立了卵清蛋白/脂多糖(OVA/LPS)诱导的SRA小鼠模型,以评估HVO对SRA的治疗效果。应用 UPLC-QE-Orbitrap-MS 分析了 HVO 的血清成分。采用网络药理学和分子对接技术揭示了HVO治疗SRA的复杂机制,并预测了HVO中潜在的有效化合物。此外,还对SRA小鼠进行了体内研究,并利用HL-60细胞和骨髓中性粒细胞进行了体外研究,以验证其机制:结果:HVO 能明显改善 OVA/LPS 诱导的 SRA 症状,包括气道高反应性、气道炎症、粘液过度分泌和气道重塑。在含有 HVO 的血清中发现了 41 种原型化合物、65 种 I 期代谢物和 50 种 II 期代谢物。将网络药理学与实验验证相结合,发现 HVO 可通过靶向中性粒细胞弹性蛋白酶抑制 NET 的形成,从而对 SRA 发挥治疗作用。同时,分子对接结果显示,3-甲氧基-4-羟基扁桃腈、1,2,3,4-四氢-1,5,7-三甲基萘、顺式菖蒲烯和马兜铃-1(10)-烯-9-基异戊酸酯可能是HVO治疗SRA的化合物:这些研究结果表明,HVO 可通过靶向 NETs 的形成来治疗中性粒细胞为主的 SRA。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Hyssopus cuspidatus volatile oil: a potential treatment for steroid-resistant asthma via inhibition of neutrophil extracellular traps.

Background: Steroid-resistant asthma (SRA) is a form of asthma resistant to corticosteroid therapy, which is characterized by the presence of neutrophil-predominant inflammatory response and neutrophil extracellular traps (NETs) formation. Hyssopus cuspidatus Boriss., a traditional Uyghur medicine, is known for its efficacy in treating inflammatory lung conditions such as asthma. However, the therapeutic impact and underlying mechanisms of Hyssopus cuspidatus Boriss.'s volatile oil (HVO) in SRA have not been fully elucidated.

Methods: This study established an ovalbumin/lipopolysaccharide (OVA/LPS)-induced SRA mice model to evaluate the therapeutic effect of HVO on SRA. UPLC-QE-Orbitrap-MS was applied to analyze the serum compositions of HVO. Network pharmacology and molecular docking were employed to uncover the complex mechanisms of HVO in treating SRA and predict potential effective compounds in HVO. Furthermore, in vivo studies in SRA mice and in vitro studies using HL-60 cells and bone marrow neutrophils were conducted to validate the mechanism.

Results: HVO could significantly ameliorate OVA/LPS-induced SRA symptoms, including airway hyperresponsiveness, airway inflammation, mucus overproduction and airway remodeling. 41 prototype compounds, 65 Phase I metabolites and 50 Phase II metabolites were identified in serum-containing HVO. The integration of network pharmacology with experimental validation revealed that HVO can inhibit the formation of NETs by targeting neutrophil elastase, thereby exerting a therapeutic influence on SRA. Meanwhile, molecular docking results showed that 3-methoxy-4-hydroxy mandelonitrile, 1,2,3,4-tetrahydro-1,5,7-trimethyl-naphthalene, cis-calamenene and aristol-1(10)-en-9-yl isovalerate may be the therapeutic compounds of HVO in treating SRA.

Conclusion: These findings suggest that HVO is a promising therapeutic candidate for neutrophil-dominant SRA by targeting NETs formation.

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来源期刊
Chinese Medicine
Chinese Medicine INTEGRATIVE & COMPLEMENTARY MEDICINE-PHARMACOLOGY & PHARMACY
CiteScore
7.90
自引率
4.10%
发文量
133
审稿时长
31 weeks
期刊介绍: Chinese Medicine is an open access, online journal publishing evidence-based, scientifically justified, and ethical research into all aspects of Chinese medicine. Areas of interest include recent advances in herbal medicine, clinical nutrition, clinical diagnosis, acupuncture, pharmaceutics, biomedical sciences, epidemiology, education, informatics, sociology, and psychology that are relevant and significant to Chinese medicine. Examples of research approaches include biomedical experimentation, high-throughput technology, clinical trials, systematic reviews, meta-analysis, sampled surveys, simulation, data curation, statistics, omics, translational medicine, and integrative methodologies. Chinese Medicine is a credible channel to communicate unbiased scientific data, information, and knowledge in Chinese medicine among researchers, clinicians, academics, and students in Chinese medicine and other scientific disciplines of medicine.
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