The Effect of Dendrobium officinale Polysaccharides on Cigarette Smoke-induced Mucus Hypersecretion in vitro and in vivo

Abstract

Background: Chronic obstructive pulmonary disease (COPD) is one of the leading causes of death worldwide, in which cigarette smoke (CS) is the major risk factor. Dendrobium officinale polysaccharide (DOP) is the main active ingredient extracted from Dendrobium officinale, which have been reported to inhibit mucin gene expression. This study aimed to investigate the effect of DOP on cigarette smoke-induced mucus hypersecretion. Methods: For in vivo study, equal numbers (n=8) of 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 daily water as control, two doses of DOP (100 mg/kg and 200 mg/kg b.wt) or N-acetylcysteine (NAC; 500 mg/kg b.wt, as positive control) via oral gavage for the remaining duration. Lung tissues were collected after sacrifice for qPCR analysis. For in vitro study, primary normal human bronchial epithelial (NHBE) cells differentiated at the air-liquid interface (ALI) for 28 days were stimulated with cigarette smoke medium (CSM) in the absence or presence of various concentrations of DOP or NAC for 24 hours (n=4). Mucus viscosity was assessed by DV2T Viscometer (AMETEK Brookfield, USA). The expression of MUC5AC was assessed by qPCR and ELISA assay. Results: CS exposure caused significant upregulation of mucin genes (MUC5AC, MUC5B and MUC2) in rat lung, which was effectively reversed by DOP or NAC. Mucus viscosity was enhanced after CSM stimulation in differentiated primary NHBE cells, which was significantly reduced by DOP in a dose-dependent manner as well as NAC. In addition, CSM-induced upregulations of MUC5AC expression at both mRNA and protein level were inhibited by DOP dose-dependently but not NAC. Conclusion: CS-induced mucus hypersecretion and viscosity could be reduced by DOP while NAC had effect only on mucus viscosity. Therefore, these findings suggest that DOP may act as a novel mucolytic drug via reduction in CS-induced mucus hypersecretion. Acknowledgement: This work was supported by Health and Medical Research Fund (HMRF) 15161911, Hong Kong SAR.