ReferenceID 977

Eucalyptol prevents bleomycin-induced pulmonary fibrosis and M2 macrophage polarization

Eur J Pharmacol

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 variou

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Reference Id
977
Evidence Id
17567
Core Evidence Id
17567
Source Reference Id
1952
Herb2 Reference Id
HBREF002749
Subject Paper Key
HBIN002102_35964659
Pubmed Id
35964659
Doi
10.1016/j.ejphar.2022.175184
Paper Title
Eucalyptol prevents bleomycin-induced pulmonary fibrosis and M2 macrophage polarization
Paper Abstract
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, krupple-like factor 4 (KLF4) and peroxisome proliferator-activated receptor gamma (PPAR-γ). These findings indicated that eucalyptol alleviates BLM-induced pulmonary fibrosis by regulating M2 macrophage polarization, which, in turn, inhibits the activation of signaling molecules (e.g., STAT6 and p38 MAPK) and the expression of transcription factors (e.g., KLF4 and PPAR-γ). Thus, eucalyptol might be a potential therapeutic agent for IPF.
Journal
Eur J Pharmacol
Publish Year
2022
Experiment Subject
Experiment Type
Animal & Cell Experiment
Phenotype Related
Pulmonary Fibrosis; Fibrosing Interstitial Pneumonia; Tumor; Lung Inflammation; Idiopathic Pulmonary Fibrosis
Paper Title Cn
Paper Title En
Eucalyptol prevents bleomycin-induced pulmonary fibrosis and M2 macrophage polarization
Bilingual Status
semi_complete