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芪卫地黄丸及其主要成分通过抑制肥大细胞脱颗粒发挥平喘作用。

Qi-Wei-Du-Qi-Wan and its major constituents exert an anti-asthmatic effect by inhibiting mast cell degranulation.

机构信息

School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, 40402, Taiwan.

Department of QC/R&D, Kaiser Pharmaceutical Co, Ltd, Tainan, 71041, Taiwan.

出版信息

J Ethnopharmacol. 2020 May 23;254:112406. doi: 10.1016/j.jep.2019.112406. Epub 2019 Nov 18.

DOI:10.1016/j.jep.2019.112406
PMID:31751647
Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

In Asia, Qi-Wei-Du-Qi-Wan (QWDQW) is a traditional Chinese medicine that has been used to treat chest tightness, cough, shortness of breath, night sweats, frequent urination and asthma. QWDQW is recorded in Yi Zong Yi Ren Pian (Medical Physician's Compilation), which was written by Yang Cheng Liu during the Qing Dynasty.

AIM OF THE STUDY

The traditional Chinese medicine QWDQW is composed of 7 ingredients and has been used in the treatment of asthma in Asia for hundreds of years. However, the mechanism through which QWDQW affects the immune system in the treatment of asthma is not known. Therefore, this study aimed to investigate whether QWDQW alleviates asthmatic symptoms in mice with chronic asthma induced by repeated stimulation with Dermatophagoides pteronyssinus (Der p) and to explore the underlying immune modulatory mechanism.

MATERIALS AND METHODS

BALB/c mice were stimulated intratracheally (i.t.) with Der p (40 μl, 2.5 μg/μl) once weekly for 6 weeks. Thirty minutes prior to Der p stimulation, the mice were treated with QWDQW (0.5 g/kg and 0.17 g/kg) orally. Three days after the last stimulation, the mice were sacrificed, and infiltration of inflammatory cells, lung histological characteristics, gene expression of lung and serum total IgE were assessed. In other experiments, RBL-2H3 cells were stimulated with DNP-IgE/DNP-BSA and then treated with QWDQW, quercetin, β-carotene, luteolin or a mixture of the three chemicals (Mix13) for 30 min, and the effects of the drugs on RBL-2H3 cell degranulation after DNP stimulation were determined.

RESULTS

QWDQW significantly reduced Der p-induced airway hyperreactivity (AHR) and decreased total serum IgE and Der p-specific IgE levels. Histopathological examination showed that QWDQW reduced inflammatory cell infiltration and sputum secretion from goblet cells in the lungs. Gene expression analysis indicated that QWDQW reduced overproduction of IL-12、IFN-γ、IL-13、IL-4、RNATES、Eotaxin and MCP-1in lung. Additionally, QWDQW and Mix13 suppressed DNP induced RBL-2H3 degranulation, and the effect was maximal when quercetin, β-carotene and luteolin were administered together.

CONCLUSION

These results indicate that QWDQW plays a role in suppressing excessive airway reaction and in specific immune modulation in a mouse model of chronic asthma and that QWDQW suppresses mast cell degranulation at defined doses of quercetin, β-carotene and luteolin.

摘要

民族药理学相关性

在亚洲,气滞胃痛丸(QWDQW)是一种传统中药,用于治疗胸闷、咳嗽、呼吸急促、盗汗、尿频和哮喘。QWDQW 记录在《医宗已任编》(Medical Physician's Compilation)中,由清代的杨成流所著。

研究目的

传统中药 QWDQW 由 7 种成分组成,已在亚洲用于治疗哮喘数百年。然而,QWDQW 影响免疫系统治疗哮喘的机制尚不清楚。因此,本研究旨在探讨 QWDQW 是否能缓解由反复变应原皮氏过敏原(Der p)刺激引起的慢性哮喘小鼠的哮喘症状,并探讨其潜在的免疫调节机制。

材料和方法

BALB/c 小鼠通过气管内(i.t.)滴注 Der p(40μl,2.5μg/μl)每周一次,共 6 周。在 Der p 刺激前 30 分钟,用 QWDQW(0.5g/kg 和 0.17g/kg)口服给药。最后一次刺激后 3 天,处死小鼠,评估炎症细胞浸润、肺组织学特征、肺和血清总 IgE 的基因表达。在其他实验中,用 DNP-IgE/DNP-BSA 刺激 RBL-2H3 细胞,然后用 QWDQW、槲皮素、β-胡萝卜素、木犀草素或三者混合物(Mix13)处理 30min,测定药物对 DNP 刺激后 RBL-2H3 细胞脱颗粒的影响。

结果

QWDQW 显著降低了 Der p 诱导的气道高反应性(AHR),降低了总血清 IgE 和 Der p 特异性 IgE 水平。组织病理学检查显示,QWDQW 减少了炎症细胞浸润和肺内杯状细胞的痰液分泌。基因表达分析表明,QWDQW 减少了 IL-12、IFN-γ、IL-13、IL-4、RNATES、Eotaxin 和 MCP-1 在肺中的过度产生。此外,QWDQW 和 Mix13 抑制 DNP 诱导的 RBL-2H3 脱颗粒,当槲皮素、β-胡萝卜素和木犀草素同时给药时,效果最大。

结论

这些结果表明,QWDQW 在慢性哮喘小鼠模型中具有抑制过度气道反应和特异性免疫调节的作用,并且 QWDQW 以特定剂量的槲皮素、β-胡萝卜素和木犀草素抑制肥大细胞脱颗粒。

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