母母-川贝母对通过调节花生四烯酸途径减轻卵清蛋白诱导的哮喘。

IF 5.1 2区 医学 Q1 CHEMISTRY, MEDICINAL
Drug Design, Development and Therapy Pub Date : 2025-05-27 eCollection Date: 2025-01-01 DOI:10.2147/DDDT.S514891
Xi Tian, Qingfei Cui, Jinhuan Wei, Qian Zhang, Huiyi Zhang, Mengxin Yang, Yiqi Xing, Yukun Niu, Wenyu Li, Nan Wang, Yiran Jin, Yingfeng Du
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引用次数: 0

摘要

背景:中药中,浙母(Anemarrhena asphodeloides Bunge, ZM) -川北母(贝母肝硬化球,CBM) (ZC)是治疗哮喘等肺部疾病最经典的中药组合之一。本研究旨在探讨ZC对哮喘的影响及其作用机制。方法:用卵清蛋白致敏哮喘模型大鼠。通过肺功能、病理切片及生化指标分析,评价ZM、CBM、ZC抗哮喘疗效。以UHPLC-QTOF-MS为基础进行代谢组学研究,以确定联合治疗的协同抗哮喘作用。应用网络药理学方法进行哮喘靶点及机制预测。然后利用RT-qPCR技术探讨ZC的潜在抗哮喘机制。结果:肺功能试验、苏木精-伊红染色实验显示,中药对抗哮喘作用明显优于中药对或中药对。ZC对Th1/Th2免疫失衡也有积极作用。代谢组学和网络药理学都高度富集了花生四烯酸代谢途径。通过RT-qPCR,花生四烯酸代谢关键靶点ALOX5、PLA2G4A和CYP1A2的mRNA表达水平显著下调。结论:ZC通过降低花生四烯酸代谢途径介导的细胞因子和趋化因子的表达,在体内可减轻ova诱导的哮喘。这是首次证明ZC治疗哮喘的复杂机制。同时,建立了基于多机制评价中药治疗哮喘药理作用的新范式。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Anemarrhena asphodeloides Bunge-Fritillaria Cirrhosae Bulbus Herb Pair Alleviates Ovalbumin-Induced Asthma by Regulating Arachidonic Acid Pathway.

Background: In traditional Chinese Medicine (TCM), Zhimu (Anemarrhena asphodeloides Bunge, ZM) - Chuanbeimu (Fritillaria Cirrhosae Bulbus, CBM) (ZC) is one of the most classical herb pairs used in the treatment of lung diseases such as asthma. This study aimed to investigate how ZC affects asthma and its mechanism.

Methods: Asthma model rats were sensitized by ovalbumin. The anti-asthma efficacy of ZM, CBM and ZC were evaluated through analysis of lung function, pathological sections and biochemical indices. Metabolomics based on UHPLC-QTOF-MS was conducted to determine the synergistic anti-asthma effect of combination therapy. Asthma targets and mechanism prediction were performed using network pharmacology. Then, the potential anti-asthma mechanism of ZC was explored using RT-qPCR.

Results: According to the lung function test, Hematoxylin-Eosin Staining experiment, ZC herb pair had an obvious anti-asthma effect over either ZM or CBM alone. It has also been demonstrated that positive effect of ZC against Th1/Th2 immune imbalance. Both metabolomics and network pharmacology were highly enriched in the arachidonic acid metabolism pathway. The mRNA expression levels of ALOX5, PLA2G4A and CYP1A2, critical targets in arachidonic acid metabolism, were significantly down-regulated by RT-qPCR.

Conclusion: By reducing the expression of cytokines and chemokines mediated by the arachidonic acid metabolism pathway, ZC could alleviate OVA-induced asthma in vivo. It was the first to demonstrate the complex mechanism of ZC for the treatment of asthma. Meanwhile, a new paradigm was established for evaluating the pharmacological effects of TCM drugs for asthma based on multiple mechanisms.

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来源期刊
Drug Design, Development and Therapy
Drug Design, Development and Therapy CHEMISTRY, MEDICINAL-PHARMACOLOGY & PHARMACY
CiteScore
9.00
自引率
0.00%
发文量
382
审稿时长
>12 weeks
期刊介绍: Drug Design, Development and Therapy is an international, peer-reviewed, open access journal that spans the spectrum of drug design, discovery and development through to clinical applications. The journal is characterized by the rapid reporting of high-quality original research, reviews, expert opinions, commentary and clinical studies in all therapeutic areas. Specific topics covered by the journal include: Drug target identification and validation Phenotypic screening and target deconvolution Biochemical analyses of drug targets and their pathways New methods or relevant applications in molecular/drug design and computer-aided drug discovery* Design, synthesis, and biological evaluation of novel biologically active compounds (including diagnostics or chemical probes) Structural or molecular biological studies elucidating molecular recognition processes Fragment-based drug discovery Pharmaceutical/red biotechnology Isolation, structural characterization, (bio)synthesis, bioengineering and pharmacological evaluation of natural products** Distribution, pharmacokinetics and metabolic transformations of drugs or biologically active compounds in drug development Drug delivery and formulation (design and characterization of dosage forms, release mechanisms and in vivo testing) Preclinical development studies Translational animal models Mechanisms of action and signalling pathways Toxicology Gene therapy, cell therapy and immunotherapy Personalized medicine and pharmacogenomics Clinical drug evaluation Patient safety and sustained use of medicines.
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