Atractylodin Suppresses TGF-β-Mediated Epithelial-Mesenchymal Transition in Alveolar Epithelial Cells and Attenuates Bleomycin-Induced Pulmonary Fibrosis in Mice

Abstract

Idiopathic pulmonary fibrosis (IPF) is characterized by fibrotic change in alveolar epithelial cells and leads to the irreversible deterioration of pulmonary function. Transforming growth factor-beta 1 (TGF-β1)-induced epithelial-mesenchymal transition (EMT) in type 2 lung epithelial cells contributes to excessive collagen deposition and plays an important role in IPF. Atractylodin (ATL) is a kind of herbal medicine that has been proven to protect intestinal inflammation and attenuate acute lung injury. Our study aimed to determine whether EMT played a crucial role in the pathogenesis of pulmonary fibrosis and whether EMT can be utilized as a therapeutic target by ATL treatment to mitigate IPF. To address this topic, we took two steps to investigate: 1. Utilization of anin vitro EMT model by treating alveolar epithelial cells (A549 cells) with TGF-β1 followed by ATL treatment for elucidating the underlying pathways, including Smad2/3 hyperphosphorylation, mitogen-activated protein kinase (MAPK) pathway overexpression, Snail and Slug upregulation, and loss of E-cadherin. Utilization of an in vivo lung injury model by treating bleomycin on mice followed by ATL treatment to demonstrate the therapeutic effectiveness, such as, less collagen deposition and lower E-cadherin expression. In conclusion, ATL attenuates TGF-β1-induced EMT in A549 cells and bleomycin-induced pulmonary fibrosis in mice.

Anthelmintic nitazoxanide protects against experimental pulmonary fibrosis

“…The main manifestations of EMT are the down‐regulated epithelial phenotype and increased mesenchymal phenotype. EMT markers include the proteins associated with cell junctions (loss of the epithelial marker E‐cadherin and increase of N‐cadherin) and cytoskeletal proteins (the increase of vimentin and fibronectin) (Chang et al, 2021; Willis & Borok, 2007). TGF‐β1 is an inducer of EMT in a variety of epithelial cells.…”

Effect of Goreisan, a Traditional Japanese Medicine, on Rat Hindlimb Lymphedema

“…45) Furthermore, atractylodin, a component of Atractylodis lanceae rhizoma, decreased NO production and mRNA levels of iNOS, TNF-α, CCL2, and LCN2 in IL-1β-treated hepatocytes, 46) inhibited the increase in mRNA levels of type I and type III collagen by TGF-β1 treatment in A549 cells, and reduced bleomycin-induced pulmonary fibrosis in mice. 47) Cinnamic acid, a component of Cinnamomi Cortex, downregulated NOX2 gene expression in PMA-stimulated THP-1 cells, subsequently reducing the expression levels of inflammatory mediators, such as IL-1β, IL-8, CCL5, and cyclooxygenase (COX)-2, suggesting that it has antioxidant and anti-inflammatory effects. 48) Dehydrotumulosic acid and pachymic acid, components of Hoelen, have been shown to inhibit LTB4 release from human leukocytes.…”

Authenticating the geographic origins of Atractylodes lancea rhizome chemotypes in China through metabolite marker identification

“…Atractylodin, a heterocyclic compound, is also a major active ingredient of ALR. Numerous pharmacological experiments, both in vivo and in vitro , have demonstrated that atractylodin possesses several activities, including anti-inflammatory, anti-tumor and liver protective effects ( Tang et al., 2018 ; Chuang et al., 2019 ; Chang et al., 2021 ). In addition, our present study also identified ketones and esters.…”

“…Atractylodin has been demonstrated to have anti-tumor, anti-bacterial, anti-viral, anti-arrhythmia effects, particularly on the nervous system and alimentary canal. Thus, it has been considered as one of the major constituents of ALR ( Chae et al., 2016 ; Ma et al., 2019 ; Chang et al., 2021 ). Sesquiterpene compounds are the major bioactive agents in ALR essential oil.…”