Callicarpa japonica Thunb. attenuates cigarette smoke-induced neutrophil inflammation and mucus secretion
Graphical abstract
Introduction
Chronic obstructive pulmonary disease (COPD) is a progressive disease that makes it hard to breathe (D’Hulst et al., 2005). COPD is the sixth leading cause of chronic morbidity and mortality (Barnes, 2007), and is characterized by chronic inflammation of the airways and lung tissue as a result of exposure to inhaled irritants such as tobacco smoke (Spurzem and Rennard, 2005). Cigarette smoke (CS) is the most important etiological risk factor for the development of COPD (Li et al., 2012) and CS exposure increases inflammation of the airways and the lungs, which causes trigger the release of chemoattractant, promoting the recruitment of inflammatory cells such as neutrophils (Stampfli and Anderson, 2009, Terashima et al., 1997).
Neutrophils are one of the first-responders of inflammatory cells to migrate towards the site of inflammation and usually found in the circulation or the airway. More recently, pathology studies have identified neutrophils are the most abundant inflammatory cells present in the bronchial wall and lumen of patients with COPD (Hoenderdos and Condliffe, 2013). Airway neutrophilia correlates with the rate of decline in lung function, increasing production of mucus (Hoenderdos and Condliffe, 2013, Stanescu et al., 1996), and raised sputum neutrophil counts correlate with high-resolution computed tomography indicators of peripheral airway dysfunction in smokers (O’Donnell et al., 2004). Neutrophils infiltration and activation of lung leads to the release of granule proteins, including neutrophil elastase (NE) which contribute to structural changes and bronchial inflammation (Gernez et al., 2010).
Mucus hypersecretion is another principal characteristic in the pathogenesis of COPD and is closely associated with a reduction in lung function (Curran and Cohn, 2010, Shin et al., 2014, Voynow and Rubin, 2009). In case of prolonged/chronic exposure to toxic agent such as cigarette smoke there is continuous neutrophil activation and permanent release of the inflammatory cytokines leading to permanent mucus hypersecretion (Sadowska, 2012, Song et al., 2015). Mucins are major components of the mucus that are synthesized by the epithelial goblet cells and submucosal glands (Shin et al., 2014). Mucin 5AC (MUC5AC) is one of the major components of airway mucus and is expressed induced by a variety of stimuli, including pro-inflammatory cytokines such as tumor necrosis factor (TNF)-α and interleukin (IL)-6, reactive oxygen species (ROS) and neutrophil elastase (NE) (Val et al., 2012).
Callicarpa japonica Thunb. (CJT) is widely distributed in Korea, China and Japan, and is traditionally used as an herbal remedy for the treatment of inflammatory diseases. CJT possess a wide variety of biological activities, and the extracts of its leaves, stem, and roots are a traditional cure for the lung infection (Kim and Shin, 2004). Two major metabolites of CJT, acteoside and forsythoside B have been reported to possess wide variety of biological activities such as anti-asthmatic effects (Wei et al., 2015), anti-atherosclerotic (Chen et al., 2009), anti-septic (Jiang et al., 2012), and anti-inflammatory effects (Jing et al., 2015). Previously, we reported that CJT reduces inflammatory responses in LPS-induced acute lung injury (Shin et al., 2015b). Considering these effects of acteoside and forsythoside B, CJT is thought to be effective in COPD. However, the protective effects of CJT in COPD have not yet been evaluated in an in vivo and in vitro study. Therefore, we investigated the effects of CJT on COPD using a cigarette smoke (CS)-induced CODP murine model and cigarette smoke condensate (CSC)-stimulated H292 cells.
Section snippets
Materials
C. japonica Thunb. (Verbenaceae) was collected from Jingdingshan Mountain of Honghuagang, Zunyi, Guizhou province in China. Voucher specimen recorded as KRIBB 0045265 has been deposited in the herbarium of the Korea Research Institute of Bioscence and Biotechnolgy (KRIBB). After drying and grinding the leaves and stem of C. japonica, the powder (45 g) was added to 100 L of methanol. The extraction was done using the method of repercolation at room temperature. The extract was filtered and
CJT decreases the recruitment of neutrophils in BALF of cigarette smoke (CS)-induced COPD murine model
Given the fact that neutrophils are the most important inflammatory cells present in the bronchial wall and lumen of patients with COPD (Hoenderdos and Condliffe, 2013), the number of neutrophils was examined in the BALF. COPD mice exhibited a significant increase in the number of neutrophils in the BALF, compared with the normal controls. However, CJT-treated mice had markedly decreased numbers of neutrophils, compared with the COPD group in the BALF in a dose-dependent manner (Fig. 1A and B).
CJT reduces the production of reactive oxygen species (ROS) and BALF contents, and the activity of neutrophil elastase (NE) in BALF
Discussion
Chronic obstructive pulmonary disease (COPD) is a major and increasing global health problem that is now a leading cause of death (Barnes, 2004). Neutrophil inflammation and mucus overproduction are considered as an important characteristic of COPD. In this study, we investigated the protective effects of CJT on COPD using a cigarette smoke (CS)-induced CODP murine model and cigarette smoke condensate (CSC)-stimulated H292 cells. CJT significantly inhibited recruitment of neutrophil and
Conflict of interest
The authors declare that there are no conflicts of interest.
Acknowledgment
This work was supported by a Grant from the Ministry of Science, ICT and Future Planning (FGC 1011433) and the KRIBB Research Initiative Program (KGM 1221521) of the Republic of Korea.
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These authors contributed equally to this work.