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三叶鬼针草乙醇提取物通过抑制过敏性哮喘模型中NF-κB/p65/ERK介导的信号传导减轻肺部炎症。

Ethanolic Extract of Tridax procumbens Mitigates Pulmonary Inflammation via Inhibition of NF-κB/p65/ERK Mediated Signalling in an Allergic Asthma Model.

作者信息

Devi Kusum, Soni Sakshi, Tripathi Vineeta, Pandey Richa, Moharana Baisakhi

机构信息

Division of Pharmacology, CSIR-CDRI, Lucknow, India; Academy of Scientific & Innovative Research (AcSIR), Kamla Nehru Nagar, Ghaziabad, Uttar Pradesh, 201002, India.

Division of Pharmacology, CSIR-CDRI, Lucknow, India.

出版信息

Phytomedicine. 2022 May;99:154008. doi: 10.1016/j.phymed.2022.154008. Epub 2022 Feb 22.

DOI:10.1016/j.phymed.2022.154008
PMID:35263673
Abstract

BACKGROUND

Tridax procumbens is a traditionally used medicinal plant with high content of active phytoconstituents having anti-inflammatory activity. Accumulating evidences have shown that Tridax procumbens efficaciously diminished oxidative stress and inflammation. However the anti-inflammatory role of Tridax procumbens is not obscured in allergic asthma.

PURPOSE

Aim of this study was to decipher the anti-inflammatory role of Tridax procumbens in allergic asthma and its underlying mechanism.

METHODS

Ethanolic extract of Tridax procumbens (TP) was prepared and major phytoconstituents (flavonoids) were characterized by biochemical and UPLC/MS analysis. Rats were sensitized and challenged with environmental allergen ovalbumin (OVA) and lipopolysaccharide (LPS) to establish an allergic asthma model. Persuasive anti-inflammatory role of TP was demonstrated in vivo (100, 200 and 400 mg/kg) and in vitro (250, 125, 75 and 25 µg/ml) experiments.

RESULTS

Characterization by UPLC/MS analysis showed the presence of various bioactive flavonoids. In in vitro study, significant reduction in ROS production, apoptosis and mitochondrial dysfunction were observed in alveolar type II cells upon pre-treatment with TP (250, 125, 75 and 25 µg/ml) in a concentration-dependant manner. In vivo, TP (200 mg/kg) oral administration showed robust anti-oxidative activity. TP treatment abrogated bronchial wall thickening, immune cell infiltration and bronchial wall fibre deposition. Immunohistochemical analysis showed the diminished expression of IL-1β, IL-6 in bronchial epithelium and vascular endothelium. TP abrogated inflammation by reducing the level of inflammatory cytokines including IL-2, IFN-γ, IL-6 and MCP-1, as well as inflammatory markers including TWEAK, TNF-α, TNF-R1 and its downstream transcription factor NF-ҡB/p65 activation and its nuclear translocation. Western blot analysis of TP treated lung tissue and alveolar type II cells showed reduced phosphorylation of ERK1/2 significantly.

CONCLUSION

TP exhibited anti-inflammatory activity by inhibition of ROS production and down-regulation of NF-ҡB/ERK signalling in vitro and in vivo asthma model. Thus, TP can be envisaged as an effective anti-inflammatory agent for OVA-induced allergic asthma.

摘要

背景

三叶鬼针草是一种传统药用植物,其活性植物成分含量高,具有抗炎活性。越来越多的证据表明,三叶鬼针草能有效减轻氧化应激和炎症。然而,三叶鬼针草在过敏性哮喘中的抗炎作用尚不明确。

目的

本研究旨在阐明三叶鬼针草在过敏性哮喘中的抗炎作用及其潜在机制。

方法

制备三叶鬼针草乙醇提取物(TP),并通过生化和超高效液相色谱/质谱分析对主要植物成分(黄酮类)进行表征。用环境过敏原卵清蛋白(OVA)和脂多糖(LPS)致敏并攻击大鼠,以建立过敏性哮喘模型。在体内(100、200和400mg/kg)和体外(250、125、75和25μg/ml)实验中证明了TP具有显著的抗炎作用。

结果

超高效液相色谱/质谱分析表征显示存在多种生物活性黄酮类化合物。在体外研究中,用TP(250、125、75和25μg/ml)预处理肺泡II型细胞后,观察到活性氧生成、细胞凋亡和线粒体功能障碍显著降低,且呈浓度依赖性。在体内,口服TP(200mg/kg)显示出强大的抗氧化活性。TP治疗消除了支气管壁增厚、免疫细胞浸润和支气管壁纤维沉积。免疫组织化学分析显示支气管上皮和血管内皮中IL-1β、IL-6的表达降低。TP通过降低包括IL-2、IFN-γ、IL-6和MCP-1在内的炎性细胞因子水平以及包括TWEAK、TNF-α、TNF-R1及其下游转录因子NF-ҡB/p65激活及其核转位在内的炎症标志物,消除了炎症。对TP处理的肺组织和肺泡II型细胞进行蛋白质印迹分析显示,ERK1/2的磷酸化显著降低。

结论

在体外和体内哮喘模型中,TP通过抑制活性氧生成和下调NF-ҡB/ERK信号传导表现出抗炎活性。因此,TP可被视为一种有效的OVA诱导的过敏性哮喘抗炎剂。

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