Eucalyptol prevents bleomycin-induced pulmonary fibrosis and M2 macrophage polarization

作者：Rui Yan, Xiaojing Han, Anbang Jiang, Junfeng Hu, Miao Li, Bangzhu Liu, Feng Qian, Linian Huang · 发表于：European Journal of Pharmacology · 年份：2022 · DOI：10.1016/j.ejphar.2022.175184 · 被引用次数：56 · 研究领域：Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis、Eosinophilic Disorders and Syndromes、Chronic Obstructive Pulmonary Disease (COPD) Research

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, fibrosing interstitial pneumonia with limited therapeutic options. Eucalyptol, a terpenoid oxide isolated from eucalyptus species, reportedly exhibits various biological activities such as anti-inflammatory and antioxidant effects. In the present study, we aimed to determine whether eucalyptol could alleviate bleomycin (BLM)-induced pulmonary fibrosis and inhibit interleukin (IL)-13-induced M2 macrophage polarization. Upon treatment with eucalyptol, BLM-induced pulmonary fibrosis and lung inflammation were significantly reduced. The pulmonary neutrophil accumulation and pulmonary permeability were inhibited and the expression of hydroxyproline, alpha-smooth muscle actin, and fibronectin was significantly down-regulated. Eucalyptol also markedly inhibited the expression of arginase-1, Ym-1, IL-13, and transforming growth factor (TGF)-β1, reduced the production of IL-13, IL-6, tumor necrosis factor (TNF)-α, and attenuated the activity of TGF-β1 in bronchoalveolar lavage fluid (BALF). Furthermore, the in vitro assay revealed that eucalyptol disturbed M2 macrophage polarization and reduced the macrophage-mediated secretion of the profibrotic factor TGF-β1. Eucalyptol inhibited the nuclear location of signal transducer and activator of transcription 6 (STAT6) and the phosphorylation of STAT6 and p38 mitogen-activated protein kinase (p38 MAPK), and reduced the expression of their downstream transcription factors, kruppl...