1′-Acetoxychavicol Acetate Isolated from Alpinia galanga Ameliorates Ovalbumin-Induced Asthma in Mice

Joung-Wook Seo,Jong-Hwa Lee,Sang-Seop Han,Byeong Sik Pyo,Eun-Ji Lee,Sang-Joon Park,Bong-Hee Kim,Soon-Chang Cho,Dae-Hun Park,Thomas H Thatcher

doi:10.1371/journal.pone.0056447

Abstract

The World Health Organization reports that 235 million people are currently affected by asthma. This disease is associated with an imbalance of Th1 and Th2 cells, which results in the upregulation of cytokines that promote chronic inflammation of the respiratory system. The inflammatory response causes airway obstruction and can ultimately result in death. In this study we evaluated the effect of 1′-acetoxychavicol acetate (ACA) isolated from Alpinia galanga rhizomes in a mouse model of ovalbumin (OVA)-induced asthma. To generate the mouse model, BALB/c mice were sensitized by intraperitoneal injection of OVA and then challenged with OVA inhalation for 5 days. Mice in the vehicle control group were sensitized with OVA but not challenged with OVA. Treatment groups received dexamethasone, 25 mg/kg/day ACA, or 50 mg/kg/day ACA for 5 days. Asthma-related inflammation was assessed by bronchoalveolar lavage fluid cell counts and histopathological and immunohistochemical analysis of lung tissues. Our results showed that ACA reduced the infiltration of white blood cells (especially eosinophils) and the level of IgE in the lungs of mice challenged with OVA and suppressed histopathological changes such as airway remodeling, goblet-cell hyperplasia, eosinophil infiltration, and glycoprotein secretion. In addition, ACA inhibited expression of the Th2 cytokines interleukin (IL)-4 and IL-13, and Th1 cytokines IL-12α and interferon-γ. Because asthmatic reactions are mediated by diverse immune and inflammatory pathways, ACA shows promise as an antiasthmatic drug candidate.

Highlights

The World Health Organization reports that 235 million people are affected by asthma, which is the most common chronic disease among children
The number of eosinophils in the bronchoalveolar lavage fluid (BALF) of mice treated with 50 mg/kg/day ACA was similar to that of dexamethasone-treated mice
We examined whether ACA treatment could alter the expression of Th1/2 cytokines IL-4, IL-6, IL-12a, and IL-13 in lung tissues

Summary

Introduction

The World Health Organization reports that 235 million people are affected by asthma, which is the most common chronic disease among children. Asthma is a serious disease that can result in death if not treated properly [1] This chronic inflammatory lung disease causes bronchoconstriction, bronchial mucosal thickening from edema, eosinophilic infiltration, bronchial wall remodeling, and excessive mucus production, and can lead to airway obstruction [2,3]. The cytokine IL-6 regulates the functions of CD4 T cells and mediates asthma induction [6], whereas IL-12 regulates the Th1/Th2 balance [7] and promotes IFN-c production [8]. IL-4 and IL-13, which are key cytokines in the pathogenesis of asthma [10], are involved in airway remodeling, inflammatory processes, airway hyperresponsiveness, goblet-cell hyperplasia, eosinophil infiltration, mucus hypersecretion, and B cell activation [11,12,13,14]. IL-5 regulates the development, activation, migration, and survival of eosinophils, which are characteristic features of asthma [15]

Methods

Results

Conclusion