School of Chinese Medicine, School of Integrated Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Jiangsu Key Laboratory for High Technology Research of TCM Formulae, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
J Ethnopharmacol. 2021 Jan 10;264:113342. doi: 10.1016/j.jep.2020.113342. Epub 2020 Sep 3.
Cough variant asthma (CVA) is characterized with its long-lasting cough symptom on clinic. The mechanism of CVA is related to chronic persistent airway inflammation, airway hyperresponsiveness, etc. The traditional Chinese prescription has achieved good curative effect on CVA treatment through reducing cough counts, decreasing airway hyperresponsiveness and alleviating airway inflammation. The mechanism is associated with reducing IL4, IL-13, NGF and CGRP levels, as well as down-regulating TRPA1/TRPV1/TRPV5 channels in both lung and brain tissues.
The Chinese prescription, San'ao decoction with scorpio and bombyx batryticatus (SSB), is well known in treating cough in asthmatic patients. In this study, the anti-tussive and anti-asthmatic role of SSB, as well as its mechanism on CVA mice model were explored and evaluated via alleviating airway inflammation and regulation of TRP channels.
The major chemical components in SSB were detected and analyzed by UPLC-QTOF-MS under an optimized chromatographic and MS condition. 60 BALB/c mice were randomly divided into six groups: normal group, model group, dexamethasone group (0.1178 mg/kg/d), SSB high dose group (9.74 g/kg/d), SSB middle dose group (4.87 g/kg/d) and SSB low dose group (2.435 g/kg/d). The cough variant asthma mice model was established by ovalbumin sensitization and challenge. The protective role of SSB on CVA mice model was studied through inducing cough counts by capsaicin, assessing inflammatory cells in peripheral blood and bronchoalveolar lavage fluid (BALF), measuring airway responsiveness, detecting histopathological changes in lung tissues, analyzing cytokines and neuropeptides levels in BALF, as well as examining the mRNA and protein expressions of TRPA1, TRPV1 and TRPV5 in both lung and brain tissues.
17 signal peaks of the chemical components in SSB were identified by using UPLC-QTOF-MS. SSB (especially the high dose and middle dose), showed significantly effects on mice model by reducing mice cough counts (P < 0.01), decreasing eosinophil (EOS) counts in blood (P < 0.01) and inflammatory cell numbers in BALF (P < 0.01), decreasing airway hyperresponsiveness (P < 0.05), reducing the levels of IL-4 (P < 0.05), IL-13 (P < 0.01), NGF (P < 0.01) and CGRP (P < 0.01) in BALF, as well as down regulating the mRNA and protein expressions of TRPA1, TRPV1 and TRPV5 in both lung and brain tissues (P < 0.01).
SSB showed anti-tussive and anti-asthmatic effects on cough variant asthma mice model by reducing cough counts, improving lung function, alleviating lung injury and airway inflammation. The mechanism of SSB might be associated with the regulation of cytokines and neuropeptides in BALF, as well as the regulation of TRPA1, TRPV1, TRPV5 channels in both lung and brain tissues.
咳嗽变异型哮喘(CVA)的临床特征为长期咳嗽。CVA 的发病机制与慢性持续性气道炎症、气道高反应性等有关。中药方剂通过减少咳嗽次数、降低气道高反应性和缓解气道炎症,对 CVA 治疗取得了良好的疗效。其作用机制与降低 IL4、IL-13、NGF 和 CGRP 水平以及下调肺和脑组织中的 TRPA1/TRPV1/TRPV5 通道有关。
三拗汤加蝎子和僵蚕(SSB)在治疗哮喘患者咳嗽方面已有一定的疗效。本研究通过减轻气道炎症和调节 TRP 通道,探讨和评价 SSB 对 CVA 小鼠模型的镇咳和平喘作用及其机制。
采用 UPLC-QTOF-MS 在优化的色谱和 MS 条件下检测和分析 SSB 中的主要化学成分。将 60 只 BALB/c 小鼠随机分为六组:正常组、模型组、地塞米松组(0.1178mg/kg/d)、SSB 高剂量组(9.74g/kg/d)、SSB 中剂量组(4.87g/kg/d)和 SSB 低剂量组(2.435g/kg/d)。卵清蛋白致敏和攻击建立咳嗽变异型哮喘小鼠模型。通过辣椒素诱导咳嗽次数、检测外周血和支气管肺泡灌洗液(BALF)中的炎症细胞、测量气道反应性、检测肺组织的组织病理学变化、分析 BALF 中细胞因子和神经肽水平以及检测肺和脑组织中 TRPA1、TRPV1 和 TRPV5 的 mRNA 和蛋白表达,研究 SSB 对 CVA 小鼠模型的保护作用。
通过 UPLC-QTOF-MS 鉴定出 SSB 中的 17 个化学成分信号峰。SSB(尤其是高剂量和中剂量)通过减少小鼠咳嗽次数(P <0.01)、降低血液中嗜酸性粒细胞(EOS)计数(P <0.01)和 BALF 中炎症细胞数量(P <0.01)、降低气道高反应性(P <0.05)、降低 IL-4(P <0.05)、IL-13(P <0.01)、NGF(P <0.01)和 CGRP(P <0.01)水平,以及下调肺和脑组织中 TRPA1、TRPV1 和 TRPV5 的 mRNA 和蛋白表达(P <0.01),对咳嗽变异型哮喘小鼠模型表现出明显的镇咳和平喘作用。
SSB 通过减少咳嗽次数、改善肺功能、减轻肺损伤和气道炎症,对咳嗽变异型哮喘小鼠模型具有镇咳和平喘作用。SSB 的作用机制可能与 BALF 中细胞因子和神经肽的调节以及肺和脑组织中 TRPA1、TRPV1、TRPV5 通道的调节有关。