Abstract
Jianpiyifei II granules (JPYF II), a herbal formula, are used for the treatment of chronic obstructive pulmonary disease (COPD) in Guangdong Provincial Hospital of Chinese Medicine. The protective effects of JPYF II against bronchial epithelial cell apoptosis in mice exposed to cigarette smoke (CS) and apoptosis of human bronchial epithelial cell lines (BEAS-2B and 16-HBE) stimulated with cigarette smoke extract (CSE) were investigated. Mice were exposed to CS generated from four cigarettes/day for 30 days and administered a dose of JPYF II (0.75, 1.5, and 3 g/kg/d) from the 3rd week of CS exposure. In mice exposed to CS, JPYF II significantly inhibited CS-induced apoptosis and overexpression of endoplasmic reticulum (ER) stress-related markers in bronchial epithelial cells of the lung tissues. In CSE-stimulated BEAS-2B and 16-HBE cells, JPYF II attenuated apoptosis and cell cycle arrest in the G0/G1 phase. Mechanistically, CSE initially induced intracellular reactive oxygen species (ROS) production, which then triggered ER stress, leading to the release of Ca2+ from ER inositol trisphosphate receptor (IP3R)-mediated stores and finally cell death. Treatment with JPYF II resulted in a significant reduction in CSE-induced apoptosis through interruption of the ROS-ER stress-Ca2+ signaling pathway. Therefore, the results of this study have revealed the underlying mechanism of action of JPYF II in the treatment of COPD.
Highlights
Chronic obstructive pulmonary disease (COPD) is a progressive disorder characterized by emphysema and chronic bronchitis resulting in the destruction of pulmonary parenchyma and narrowing of the airways (Papandrinopoulou et al, 2012; Wei et al, 2013; Yu et al, 2015)
Compared with the control group (3.94% ± 3.25%), the number of TransferaseMediated dUTP Nick End Labeling (TUNEL)-positive cells was greater in the bronchial epithelium of mice exposed to cigarette smoke (CS) (73.54% ± 4.34%), while the proportion of TUNEL-positive cells in the Jianpiyifei II granules (JPYF II) treatment groups was lower than that of the model group (Figures 1A, B)
Immunohistochemical staining revealed that expression of glucose-regulated protein 78 (GRP78), phosphorylation of eukaryotic initiation factor 2a and CCAAT-enhancer-binding protein homologous protein (CHOP) in bronchial epithelial cells in the control group was quite low, but significantly greater in cells from the model group, and considerably less in the JPYF II treatment groups than in the model group (Figure 1C)
Summary
Chronic obstructive pulmonary disease (COPD) is a progressive disorder characterized by emphysema and chronic bronchitis resulting in the destruction of pulmonary parenchyma and narrowing of the airways (Papandrinopoulou et al, 2012; Wei et al, 2013; Yu et al, 2015). Through the detection of proteins characteristic of the UPR, including glucose-regulated protein 78 (GRP78), calreticulin and calnexin, ER stress has been shown to occur in patients with COPD (Min et al, 2011; Ribeiro and O’Neal, 2012) These UPR proteins have been shown to be upregulated in chronic smokers in comparison with nonsmokers (Kelsen et al, 2008), indicating a plausible role for ER stress and UPR activation in smoking, possibly resulting in cell death, and disease (Jorgensen et al, 2008; Kamp et al, 2013)
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