Linggan Wuwei Jiangxin formula ameliorates airway hyperresponsiveness through suppression of IL-1β and IL-17A expression in allergic asthmatic mice especially with diet-induced obesity.
Linggan Wuwei Jiangxin formula ameliorates airway hyperresponsiveness through suppression of IL-1β and IL-17A expression in allergic asthmatic mice especially with diet-induced obesity.
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DOI：
10.21037/atm-21-1189
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发表时间：
2021-04
影响因子：
--
通讯作者：
Lu Z
中科院分区：
文献类型：
--
作者：
Ma Z;Li C;Xue L;Zhang S;Yang Y;Zhang H;Lu Z
肥胖哮喘代表了一种疾病表型，它与较差的疾病控制和对标准抗炎方案（包括吸入皮质类固醇）的无反应有关。肥胖相关的先天气道高反应性（AHR）通过激活IL-1β/先天淋巴样细胞3 (ILC3)/IL-17A通路在这种哮喘表型中发挥作用。从中医理论、临床经验及相关研究来看，灵感五味降心方可能是治疗肥胖性哮喘的理想选择。采用卵清蛋白（OVA）致敏和高脂饮食（HFD）联合攻毒法建立小鼠过敏性哮喘伴肥胖模型。口服LGWWJX方干预。测定AHR和支气管肺泡灌洗液（BALF）细胞量。采用血红素和伊红（H&E）染色进行肺、肝组织病理学检查。ELISA法检测BALF和血清中IL-1β和IL-17A含量。此外，我们在体外研究了不同浓度的LGWWJX配方对IL-1β刺激的ILC3细胞IL-17A mRNA表达的影响。通过肺组织病理学和BALF细胞水平测量，LGWWJX治疗显著降低了哮喘小鼠的AHR和过敏性气道炎症反应，并且这些作用在肥胖哮喘小鼠中更为明显。在非肥胖哮喘小鼠中，LGWWJX能抑制BALF中嗜酸性粒细胞的浸润，而在肥胖哮喘小鼠中，中性粒细胞和嗜碱性粒细胞明显减少。值得注意的是，LGWWJX在喂食HFD的小鼠中也表现出了显著的减肥和改善肝脏脂肪变性的功效。此外，在肥胖和非肥胖哮喘小鼠中，LGWWJX干预后，血清和BALF中IL-1β的蛋白水平以及BALF中IL-17A的蛋白水平均下降，离体实验结果发现LGWWJX在IL-1β刺激或不刺激的情况下显著降低ILC3细胞中IL-17A的表达。LGWWJX可能对哮喘个体，特别是并发肥胖的个体发挥保护作用，其机制可能包括抑制IL-1β/ILC3/IL-17A/AHR轴、抗炎作用、体重减轻和调节脂质代谢。这表明LGWWJX单独或与抗炎药联合治疗肥胖哮喘具有良好的作用。
Obese asthma represents a disease phenotype, which is associated with worse disease control and unresponsiveness to standard anti-inflammatory regimens, including inhaled corticosteroids. Obesity-related innate airway hyperresponsiveness (AHR) plays a role in this asthma phenotype via activation of the IL-1β/innate lymphoid cell 3 (ILC3)/IL-17A pathway. Linggan Wuwei Jiangxin (LGWWJX) formula may be a promising therapeutic option for obese asthma according to traditional Chinese medicine theory, clinical experience and related research. The murine model of allergic asthma with obesity was induced by ovalbumin (OVA) sensitization and challenge in combination with a high fat diet (HFD). LGWWJX formula intervention was oral administrated. AHR and bronchoalveolar lavage fluid (BALF) cellularity were measured. Lung and liver histopathology assessment was performed by haematoxylin and eosin (H&E) staining. IL-1β and IL-17A in BALF and serum were evaluated by ELISA. Additionally, the influence of different concentrations of LGWWJX formula on IL-1β stimulated IL-17A mRNA expression in ILC3 cells was evaluated in vitro. LGWWJX treatment significantly reduced AHR and allergic airway inflammatory responses in asthmatic mice, as measured by pulmonary histopathology and BALF cellularity, and these effects were more pronounced in obese asthmatic mice. While eosinophil infiltration in BALF was suppressed with LGWWJX treatment in non-obese asthmatic mice, neutrophils and basophils were significantly decreased in obese asthmatic mice. Notably, LGWWJX also demonstrated remarkable efficacy for weight loss and improvements in hepatic steatosis in mice fed with a HFD. Furthermore, the protein levels of IL-1β in both serum and BALF, as well as those of BALF IL-17A, declined with LGWWJX intervention in both obese and non-obese asthmatic mice, and results from ex-vivo experiments found that LGWWJX significantly attenuated the expression of IL-17A in ILC3 cells with or without stimulation by IL-1β. LGWWJX may exert a protective effect on asthmatic individuals, especially those with concurrent obesity, most likely through mechanisms including the inhibition of the IL-1β/ILC3/IL-17A/AHR axis, anti-inflammatory effects, weight loss, and the regulation of lipid metabolism. This suggests a promising role of LGWWJX, alone or in combination with anti-inflammatory agents, for the treatment of obese asthma.
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姜的6个shogaol提取物上调细胞和小鼠的抗氧化剂防御系统。
DOI：
10.3390/molecules17078037
发表时间：
2012-07-04
期刊：
Molecules (Basel, Switzerland)
影响因子：
--
作者：
Bak MJ;Ok S;Jun M;Jeong WS
通讯作者：
Jeong WS
影响因子：
32.4
作者：
Guo, Xiaohuan;Qiu, Ju;Tu, Tony;Yang, Xuanming;Deng, Liufu;Anders, Robert A.;Zhou, Liang;Fu, Yang-Xin
通讯作者：
Fu, Yang-Xin
影响因子：
3.2
作者：
Williams AS;Chen L;Kasahara DI;Si H;Wurmbrand AP;Shore SA
通讯作者：
Shore SA
DOI：
10.1164/rccm.200702-323oc
发表时间：
2007-10-01
影响因子：
24.7
作者：
Johnston, Richard A.;Zhu, Ming;Shore, Stephanie A.
通讯作者：
Shore, Stephanie A.
影响因子：
6.1
作者：
Scott, H. A.;Gibson, P. G.;Wood, L. G.
通讯作者：
Wood, L. G.