Abstract

Chronic obstructive pulmonary disease (COPD), characterized by oxidative stress and inflammation, is one of the leading causes of death worldwide, in which cigarette smoke (CS) is the major risk factor. Dendrobium officinale polysaccharides (DOPs) are the main active ingredients extracted from Dendrobium officinale, which have been reported to have antioxidant and anti-inflammatory activity as well as inhibition of mucin gene expression. This study is aimed at investigating the effect of DOPs on CS-induced mucus hypersecretion and viscosity in vitro and in vivo. For in vitro study, primary normal human bronchial epithelial cells (HBECs) differentiated at the air-liquid interface (ALI) culture for 28 days were stimulated with cigarette smoke medium (CSM) in the absence or presence of various concentrations of DOPs or N-acetylcysteine (NAC) for 24 hours. For in vivo study, male Sprague-Dawley rats were randomized to sham air (SA) as control group or CS group for 56 days. At day 29, rats were subdivided and given water as control, DOPs, or NAC as positive control as a mucolytic drug via oral gavage for the remaining duration. Samples collected from apical washing, cell lysates, bronchoalveolar lavage (BAL), and lung tissues were evaluated for mucin gene expression, mucus secretion, and viscosity. DOPs ameliorated the CS-induced mucus hypersecretion and viscosity as shown by the downregulation of MUC5AC mRNA, MUC5AC secretary protein, and mucus viscosity via inhibition of mucus secretory granules in both in vitro and in vivo models. DOPs produced its effective effects on the CS-induced mucus hypersecretion and viscosity via the inhibition of the mucus secretory granules. These findings could be a starting point for considering the potential role of DOPs in the management of the smoking-mediated COPD. However, further research is needed.

Highlights

  • Chronic obstructive pulmonary disease (COPD), which is characterized by persistent airflow limitation and airway inflammation, is the third leading cause of death globally [1]

  • The airway epithelial surface is covered by mucus, which is an extracellular gel with two major components, water and mucins, protecting the lung from continuous environmental exposure [6]

  • The viscosity of mucus is determined by mucus solid concentration, increased mucus viscosity led to disability of cilia clearance [8]

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Summary

Introduction

Chronic obstructive pulmonary disease (COPD), which is characterized by persistent airflow limitation and airway inflammation, is the third leading cause of death globally [1]. Cigarette smoke (CS), as the major risk factor for COPD, has been reported to be associated with chronic airway inflammation, airway epithelium impairment, and mucus hypersecretion [2,3,4]. The airway epithelial surface is covered by mucus, which is an extracellular gel with two major components, water and mucins, protecting the lung from continuous environmental exposure [6]. Mucin-5AC (MUC5AC) is the major gel-forming mucin in proximal airways by surface goblet cells, which are the predominant subtype found in COPD patients [9]. Cigarette smoke activates EGFRs which activate mitogen-activated protein (MAP) kinases and cause upregulation of mucin MUC5AC in airway epithelial cells and led to mucus hypersecretion [12].

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