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五味子醇甲通过调节NF-κB/IκBα和Nrf2/HO-1信号通路减轻小鼠过敏性哮喘

Schisandrol A Alleviates Allergic Asthma in Mice via Regulating the NF-κB/IκBα and Nrf2/HO-1 Signaling Pathways.

作者信息

Dong Yang, Zou Yi-Zhuo, Li Ting, Sun Jing-Hui, Li He, Zhuang Wen-Yue, Song Yan, Wang Chun-Mei

机构信息

Department of Pharmacology, School of Pharmacy, Beihua University, Jilin, China.

Department of Molecular Biology Test Technique, School of Medical Technology, Beihua University, Jilin, China.

出版信息

J Med Food. 2025 Jan;28(1):28-37. doi: 10.1089/jmf.2024.k.0117. Epub 2024 Sep 24.

Abstract

(Turcz) Baill () is the key traditional Chinese medicine for the treatment of asthma used by ancient and modern medical practitioners. However, the material basis and the main mechanism of its antiasthmatic effect remain unclear. Our preliminary results showed that schisandrol A (SCA), a representative monomer of lignans, had the best relaxation effect on tracheal rings in isolated rats. In this research, a mouse asthma model was prepared by combining ovalbumin (OVA) with Al (OH) for exploring the antiasthmatic action and the underlying mechanism of SCA. The study results demonstrated that SCA improved the behavior of mice with asthma and pathological changes in their lung tissues and airways, decreased serum immunoglobulin E (IgE) and OVA-IgE levels, interleukin-4 (IL-4), IL-5, IL-13, and eotaxin contents, and leukocytes number in bronchoalveolar lavage fluid. SCA downregulated the gene expressions of keratinocyte-derived protein chemokines and ILs and reduced the expressions of phosphorylated IκB kinase α (p-IKKα) and p-nuclear factor kappa-B (NF-κB) proteins in lung tissues. In addition, it was found that SCA could significantly increase T-superoxide dismutase and catalase activities, decrease malondialdehyde content, and elevate p-IκBα, NF-E2-related-factor 2 (Nrf2), and heme oxygenase-1 (HO-1) protein expressions. In summary, SCA treatment resulted in a significant improvement in the allergic bronchial asthma in mice, and its mechanisms may involve the regulation of the NF-κB/IκBα pathway to reduce inflammatory response and the Nrf2/HO-1 pathway to improve the body's antioxidant capacity. These results suggest that SCA is a key component of in exerting antiasthmatic effects.

摘要

(图尔茨)百部是古今医家治疗哮喘的关键中药。然而,其抗哮喘作用的物质基础和主要机制尚不清楚。我们的初步结果表明,木脂素的代表性单体五味子醇甲(SCA)对离体大鼠气管环具有最佳的舒张作用。本研究通过将卵清蛋白(OVA)与氢氧化铝联合使用制备小鼠哮喘模型,以探讨SCA的抗哮喘作用及其潜在机制。研究结果表明,SCA改善了哮喘小鼠的行为以及其肺组织和气道的病理变化,降低了血清免疫球蛋白E(IgE)和OVA-IgE水平、白细胞介素-4(IL-4)、IL-5、IL-13和嗜酸性粒细胞趋化因子含量,以及支气管肺泡灌洗液中的白细胞数量。SCA下调了角质形成细胞衍生的蛋白趋化因子和白细胞介素的基因表达,并降低了肺组织中磷酸化IκB激酶α(p-IKKα)和磷酸化核因子κB(NF-κB)蛋白的表达。此外,发现SCA可显著提高超氧化物歧化酶和过氧化氢酶活性,降低丙二醛含量,并提高p-IκBα、核因子E2相关因子2(Nrf2)和血红素加氧酶-1(HO-1)蛋白表达。综上所述,SCA治疗可显著改善小鼠过敏性支气管哮喘,其机制可能涉及调节NF-κB/IκBα途径以减轻炎症反应以及Nrf2/HO-1途径以提高机体抗氧化能力。这些结果表明,SCA是百部发挥抗哮喘作用的关键成分。

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