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叶下珠素和矮地茶素通过调节 IgE、Nrf2、iNOS、TNF-α 和 IL 改善卵清蛋白诱导的哮喘的免疫炎症反应。

Phyllanthin and hypophyllanthin from ameliorates immune-inflammatory response in ovalbumin-induced asthma: role of IgE, Nrf2, iNOs, TNF-α, and IL's.

机构信息

a Department of Pediatrics , The First Affiliated Hospital of Nanjing Medical University , Nanjing , Jiangsu , P.R. China.

b Department of Pediatrics , The Second Affiliated Hospital of Nanjing Medical University , Nanjing , Jiangsu , P.R. China.

出版信息

Immunopharmacol Immunotoxicol. 2019 Feb;41(1):55-67. doi: 10.1080/08923973.2018.1545788. Epub 2018 Dec 12.

Abstract

Asthma is a chronic airway immunoinflammatory disorder characterized by airway remodeling. has been reported to possess antioxidant and anti-inflammatory potential. To evaluate the possible mechanism of action of isolated phytoconstituents from (PA) against ovalbumin (OVA)-induced experimental airway hyperresponsiveness (AHR). Phyllanthin and hypophyllanthin were isolated and characterized (HPLC) from the methanolic extract of PA. AHR was induced in Sprague-Dawley rats by OVA-challenged, and animals were treated with PA (50, 100, and 200 mg/kg, p.o.) for 28 days. The HPLC analysis showed the presence of phyllanthin and hypophyllanthin in methanolic extract of PA at RT of 25.243 and 26.832 min, respectively. OVA-induced alterations in hemodynamic parameters, lung functions test, peripheral blood oxygen level, total, and differential cell count in Bronchoalveolar Lavage Fluid was significantly attenuated ( < .05) by PA (100 and 200 mg/kg). It also significantly decreased ( < .05) the levels of total protein and albumin in serum, BALF, and lungs. OVA-induced increase in IgE (total and OVA-specific), and oxido-nitrosative stress (SOD, GSH, MDA, and NO) levels were significantly ( < .05) decreased by PA. RT-PCR analysis revealed that elevated oxido-nitrosative stress (Nrf2 and iNOs), immune-inflammatory makers (HO-1, TNF-α, IL-1β, and TGF-β1), Th2 cytokines (IL-4 and IL-6) levels were significantly attenuated ( < .05) by PA. PA also attenuated histological and ultrastructural aberrations induced by OVA. Results of the present investigation demonstrated that the presence of phyllanthin and hypophyllanthin in alleviated Th2 response in OVA-induced AHR via modulation of endogenous markers in a murine model of asthma. Thus, phyllanthin and hypophyllanthin may be a new therapeutic approach for the management of asthma.

摘要

哮喘是一种慢性气道免疫炎症性疾病,其特征是气道重塑。已经报道其具有抗氧化和抗炎潜力。为了评估从 (PA) 分离的植物化合物对卵清蛋白(OVA)诱导的实验性气道高反应性(AHR)的可能作用机制。从 PA 的甲醇提取物中分离并鉴定出叶素和隐叶素(HPLC)。通过 OVA 挑战诱导 Sprague-Dawley 大鼠 AHR,并用 PA(50、100 和 200mg/kg,口服)治疗 28 天。HPLC 分析显示,在 PA 的甲醇提取物中,叶素和隐叶素分别在 RT 为 25.243 和 26.832 分钟时存在。PA(100 和 200mg/kg)显著减弱了 OVA 诱导的血流动力学参数、肺功能试验、外周血氧水平、总细胞和支气管肺泡灌洗液中的分类细胞计数的改变(<0.05)。它还显著降低了血清、BALF 和肺中总蛋白和白蛋白的水平(<0.05)。PA 还显著降低了 IgE(总和 OVA 特异性)和氧化应激(SOD、GSH、MDA 和 NO)水平的增加。RT-PCR 分析显示,升高的氧化应激(Nrf2 和 iNOs)、免疫炎症标志物(HO-1、TNF-α、IL-1β 和 TGF-β1)、Th2 细胞因子(IL-4 和 IL-6)水平被 PA 显著减弱(<0.05)。PA 还减轻了 OVA 诱导的组织学和超微结构异常。本研究结果表明,PA 中存在的叶素和隐叶素通过调节哮喘小鼠模型中的内源性标志物,减轻了 OVA 诱导的 AHR 中的 Th2 反应。因此,叶素和隐叶素可能是治疗哮喘的新方法。

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