Spiraea prunifolia var. simpliciflora Attenuates Oxidative Stress and Inflammatory Responses in a Murine Model of Lipopolysaccharide-Induced Acute Lung Injury and TNF-α-Stimulated NCI-H292 Cells.

Ba-Wool Lee,Da-Bin Jeon,Hyeon-Young Kim,Woo-Song Lee,Hyun-Jae Jang,Han-Gyo Shin,Ju-Hong Kim,In-Chul Lee,Young-Bae Ryu,Ji-Hye Ha,Kyungsook Jung,Seong-Hun Jeong,Hyung-Jun Kwon,Ji-Young Park,Sung-Hwan Kim

doi:10.3390/antiox9030198

Abstract

Spiraea prunifolia var. simpliciflora (SP) is traditionally used as an herbal remedy to treat fever, malaria, and emesis. This study aimed to evaluate the anti-oxidative and anti-inflammatory properties of the methanol extract of SP leaves in tumor necrosis factor (TNF)-α-stimulated NCI-H292 cells and in a lipopolysaccharide (LPS)-induced acute lung injury (ALI) mouse model. SP decreased the number of inflammatory cells and the levels of TNF-α, interleukin (IL)-1β, and IL-6 in the bronchoalveolar lavage fluid, and inflammatory cell infiltration in the lung tissues of SP-treated mice. In addition, SP significantly suppressed the mRNA and protein levels of TNF-α, IL-1β, and IL-6 in TNF-α-stimulated NCI-H292 cells. SP significantly suppressed the phosphorylation of the mitogen-activated protein kinases (MAPKs) and p65-nuclear factor-kappa B (NF-κB) in LPS-induced ALI mice and TNF-α-stimulated NCI-H292 cells. SP treatment enhanced the nuclear translocation of nuclear factor erythroid 2-related factor (Nrf2) with upregulated antioxidant enzymes and suppressed reactive oxygen species (ROS)-mediated oxidative stress in the lung tissues of LPS-induced ALI model and TNF-α-stimulated NCI-H292 cells. Collectively, SP effectively inhibited airway inflammation and ROS-mediated oxidative stress, which was closely related to its ability to induce activation of Nrf2 and inhibit the phosphorylation of MAPKs and NF-κB. These findings suggest that SP has therapeutic potential for the treatment of ALI.

Highlights

Acute lung injury (ALI) is a severe respiratory disorder that underlies acute and persistent lung inflammation [1,2]
The major peaks that were detected in S. prunifolia extract (Figure 1 and Table 1) were tentatively identified by comparison with previously literatures, as well as accurate mass and fragmentation pattern of mass spectra acquired in negative mode
Caffeoyl quinic acid (CQA) has a molecular weight of 354 and its various regional (3, 4, and 5-CQA) and geometrical isomers were reported in many natural products [25,27]

Summary

Introduction

Acute lung injury (ALI) is a severe respiratory disorder that underlies acute and persistent lung inflammation [1,2]. It is characterized by neutrophil influx, alveolar-capillary barrier damage leading to interstitial edema, and the impairment of respiratory function [3,4]. It has been reported that Nrf plays an essential role in protecting cells against inflammatory and oxidative stress-mediated diseases [17,18]. Emerging evidence indicates that Nrf activation plays a protective role against LPS-induced oxidative stress and inflammation in the LPS-induced ALI model [14,18]

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