Andrographolide ameliorates OVA-induced lung injury in mice by suppressing ROS-mediated NF-κB signaling and NLRP3 inflammasome activation.

Shuang Peng,Wen Liu,Wenjie Guo,Yang Sun,Qiang Xu,Chunhong Jiang,Jian Gao,Xiaoling Yang

doi:10.18632/oncotarget.12918

Shuang Peng, Wen Liu + Show 6 more

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https://doi.org/10.18632/oncotarget.12918

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Journal: Oncotarget	Publication Date: Oct 26, 2016
Citations: 68	License type: cc-by

Affiliation: Nanjing University, Buchang Pharma (China)

Abstract

In this study, we attempted to explore the effect and possible mechanism of Andrographolide on OVA-induced asthma. OVA challenge induced significant airway inflammatory cell recruitment and lung histological alterations, which were ameliorated by Andrographolide. The protein levels of cytokines in bron-choalveolar fluid (BALF) and serum were reduced by Andrographolide administration as well as the mRNA levels in lung tissue. Mechanically, Andrographolide markedly hampered the activation of nuclear factor-κB (NF-κB) and NLRP3 inflammasome both in vivo and vitro thus decreased levels of TNF-α and IL-1β. Finally, we confirmed that ROS scavenging was responsible for Andrographolide's inactivation of NF-κB and NLRP3 inflammasome signaling. Our study here revealed the effect and possible mechanism of Andrographolide on asthma, which may represent a new therapeutic approach for treating this disease.

Highlights

Lung injuries and its related chronic respiratory disorders which could be death threaten, are widespread healthy problems over the world [1]
Studies have proposed that pattern recognition receptors (PRR) including TLR4 are necessary for Th2 responses upon pattern-associated molecular patterns (PAMPs) like LPS [5]
In order to verify whether Andrographolide can improve asthma, we used a mouse model of OVAinduced lung inflammation to evaluate its effect. 24 h after the last OVA aerosol challenge, the mice were sacrificed and bron-choalveolar fluid (BALF) was collected

Summary

Introduction

Lung injuries and its related chronic respiratory disorders which could be death threaten, are widespread healthy problems over the world [1]. A respiratory disorder with lung injuries, is characterized by airway inflammation and bronchial hyper-responsiveness. It was estimated in 2012 that 18 million Americans had asthma [2]. Studies have proved that NLRP3, one of NLR family membranes, has a substantial impact on tissue inflammation including respiratory diseases [1, 9, 10]. The NLRP3 inflammasome complex, which is composed by NLRP3, ASC and CASP1, contributes to recognition of unique microbial and danger components. It functions as a platform for CASP1 activation, which is responsible for IL-1β/IL18 maturation [11]. Target for NLRP3 inflammasome activation has been suggested as a useful strategy for inflammatory disease control

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