Aucubin Alleviates Chronic Obstructive Pulmonary Disease by Activating Nrf2/HO-1 Signaling Pathway.

Abstract

Background: Chronic obstructive pulmonary disease (COPD) is a common chronic respiratory disease with high death rates. Aucubin is an iridoid glycoside extracted from Eucommia ulmoides with antioxidative and anti-inflammatory properties in human diseases. This study aimed to investigate its specific function in mouse and cell models of COPD.

Methods: The COPD mouse model was established by exposing mice to a long-term cigarette smoke (CS). The number of inflammatory cells and the contents of inflammatory factors tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), and IL-8 in bronchoalveolar lavage fluid (BALF) of CS-exposed mice were measured. The levels of superoxide dismutase (SOD), glutathione (GSH), malondialdehyde (MDA), and myeloperoxidase (MPO) in the lung tissues were estimated. Masson staining and hematoxylin-eosin (H&E) staining were utilized to evaluate pulmonary fibrosis and emphysema in CS-treated mice. Cell apoptosis in the lung tissues was estimated by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay. Western blot was applied to quantify protein levels of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and apoptotic markers. COPD cell model was established by exposing mouse lung epithelial cells (MLE12) with cigarette smoke extract to further verify the properties of aucubin in vitro.

Results: Aucubin reduced the number of inflammatory cells and decreased the contents of TNF-α, IL-6, and IL-8 in BALF of CS-treated mice. The oxidative stress, lung emphysema, fibrosis, and lung cell apoptosis induced by CS exposure were ameliorated by aucubin administration. Aucubin activated the Nrf2/HO-1 signaling pathway in vitro and in vivo. Pretreatment with ML385, a specific Nrf2 inhibitor, antagonized the protective effects of aucubin on inflammation, oxidative stress, fibrosis, and cell apoptosis in COPD.

Conclusion: Aucubin alleviates inflammation, oxidative stress, apoptosis, and pulmonary fibrosis in COPD mice and CSE-treated MLE12 cells by activating the Nrf2/HO-1 signaling pathway.