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- 痰热清片通过抑制 Janus 激酶 1(JAK1)/信号转导子和转录激活子 6(STAT6)信号通路减轻过敏性哮喘。

-Tang Tablet, a Standardized Medicine Attenuates Allergic Asthma via Inhibition of Janus Kinase 1 (JAK1)/ Signal Transducer and Activator of Transcription 6 (STAT6) Signal Pathway.

机构信息

Department of Convergence Korean Medical Science, College of Korean Medicine, Kyung Hee University, Seoul 02447, Korea.

College of Pharmacy, Chonnam National University, Gwangju 61186, Korea.

出版信息

Molecules. 2020 May 8;25(9):2206. doi: 10.3390/molecules25092206.

Abstract

Exposure to particulate matter (PM) has been known to be one of the risk factors to cause allergic asthma, leading to development of respiratory disease. -tang tablet (BHT), a standardized Korean Medicine, is prescribed for neurasthenia, laryngopharyngitis and asthma. In this study, we investigated therapeutic effects of BHT on airway inflammation in ovalbumin (OVA) and PM smaller than 10 μm (PM)-induced allergic asthma mice. To establish allergic asthma with airway hyper-responsiveness by PM, BALB/c mice were sensitized and challenged with OVA and PM, and orally administered BHT. Histological staining was performed to assess airway remodeling. Serum and bronchoalveolar lavage fluid (BALF) was collected for measuring immunoglobulin levels and counting inflammatory cells, respectively. Expression levels of Janus kinase 1 (JAK1)/signal transducer and activator of transcription 6 (STAT6), pro-inflammatory cytokines and type 2 T-helper (Th2)-related cytokines were analyzed in vivo and in vitro models. Histopathological analysis demonstrated that BHT suppressed inflammatory cell infiltration, mucus hypersecretion and collagen deposition in the airway. BHT administration effectively decreased number of inflammatory cells in BALF. BHT reduced total serum Immunoglobulin E (IgE) and Immunoglobulin G (IgG) levels. In addition, BHT significantly inhibited the phosphorylation of JAK1 and STAT6 expressions. Release of pro-inflammatory cytokines and Th2-related cytokines were down-regulated by BHT. In conclusion, BHT mitigated airway inflammation by down-regulating pro-inflammatory and Th2-related cytokines via JAK1/STAT6 signaling. BHT might be a promising herbal medicine for preventing airway inflammation. Moreover, an intervention study among humans is needed to further evaluate the possible beneficial effects of BHT in allergic asthma.

摘要

颗粒物(PM)暴露已被认为是导致过敏性哮喘的危险因素之一,导致呼吸道疾病的发展。- 丹参滴丸(BHT)是一种标准化的中药,用于治疗神经衰弱、喉炎和哮喘。在这项研究中,我们研究了 BHT 对卵清蛋白(OVA)和小于 10 μm 的颗粒物(PM)诱导的过敏性哮喘小鼠气道炎症的治疗作用。为了通过 PM 建立具有气道高反应性的过敏性哮喘,BALB/c 小鼠用 OVA 和 PM 致敏和攻毒,并口服给予 BHT。进行组织学染色以评估气道重塑。收集血清和支气管肺泡灌洗液(BALF)分别用于测量免疫球蛋白水平和计数炎症细胞。在体内和体外模型中分析 Janus 激酶 1(JAK1)/信号转导和转录激活因子 6(STAT6)、促炎细胞因子和 2 型 T 辅助(Th2)相关细胞因子的表达水平。组织病理学分析表明,BHT 抑制气道中炎症细胞浸润、黏液分泌过多和胶原沉积。BHT 给药可有效减少 BALF 中的炎症细胞数。BHT 降低总血清免疫球蛋白 E(IgE)和免疫球蛋白 G(IgG)水平。此外,BHT 显著抑制 JAK1 和 STAT6 表达的磷酸化。BHT 下调促炎细胞因子和 Th2 相关细胞因子的释放。总之,BHT 通过下调 JAK1/STAT6 信号通路抑制促炎和 Th2 相关细胞因子,从而减轻气道炎症。BHT 可能是预防气道炎症的有前途的草药。此外,需要进行人群干预研究,以进一步评估 BHT 在过敏性哮喘中的可能有益作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c19d/7248972/9ce886e5098e/molecules-25-02206-g0A1.jpg

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