Antrodia cinnamomea extract alleviates bleomycin-induced pulmonary fibrosis in mice by inhibiting the mTOR pathway

Ying-Wei Lan; Chia-En Chen; Tsung-Teng Huang; Tse-Hung Huang; Chuan-Mu Chen; Kowit-Yu Chong

doi:10.1016/j.bj.2024.100720

Antrodia cinnamomea extract alleviates bleomycin-induced pulmonary fibrosis in mice by inhibiting the mTOR pathway

Biomed J. 2024 Apr 26:100720. doi: 10.1016/j.bj.2024.100720. Online ahead of print.

Authors

Ying-Wei Lan¹, Chia-En Chen², Tsung-Teng Huang², Tse-Hung Huang³, Chuan-Mu Chen⁴, Kowit-Yu Chong⁵

Affiliations

¹ Phoenix Children's Health Research Institute, University of Arizona College of Medicine-Phoenix, Phoenix, AZ, USA.
² Department of Medical Biotechnology and Laboratory Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
³ Department of Traditional Chinese Medicine, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan.
⁴ Department of Life Sciences, Agricultural Biotechnology Center, National Chung Hsing University, Taichung, Taiwan; The IEGG and Animal Biotechnology Center and the Rong Hsing Research Center for Translational Medicine, National Chung Hsing University, Taichung, Taiwan.
⁵ Department of Medical Biotechnology and Laboratory Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan; Graduate Institute of Biomedical Sciences Division of Biotechnology, Chang Gung University, Taoyuan, Taiwan; Department of Traditional Chinese Medicine, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan; Hyperbaric Oxygen Medical Research Lab, Bone and Joint Research Center, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan; Centre for Stem Cell Research, Faculty of Medicine and Health Sciences, Universiti Tunku Abdul Rahman, Selangor, Malaysia. Electronic address: kchong@mail.cgu.edu.tw.

PMID: 38679198
DOI: 10.1016/j.bj.2024.100720

Abstract

Background: Pulmonary fibrosis is a progressive diffuse parenchymal lung disorder with a high mortality rate. Studies have indicated that injured lung tissues release various pro-inflammatory factors, and produce a large amount of nitric oxide. There is also accumulation of collagen and oxidative stress-induced injury, collectively leading to pulmonary fibrosis. Antrodia cinnamomea is an endemic fungal growth in Taiwan, and its fermented extracts exert anti-inflammatory effects to alleviate liver damages. Hence, we hypothesized and tested the feasibility of using A. cinnamomea extracts for treatment of pulmonary fibrosis.

Methods: The TGF-β1-induced human lung fibroblast cells (MRC-5) in vitro cell assay were used to evaluate the effects of A. cinnamomea extracts on the collagen production in MRC-5. Eight-week-old ICR mice were intratracheally administered bleomycin and then fed with an A. cinnamomea extract on day 3 post-administration of bleomycin. At day 21 post-bleomycin administration, the pulmonary functional test, the expression level of inflammation- and fibrosis-related genes in the lung tissue, and the histopathological change were examined.

Results: The A. cinnamomea extract significantly attenuated the expression level of collagen in the TGF-β1-induced MRC-5 cells. In the A. cinnamome-treated bleomycin-induced lung fibrotic mice, the bodyweight increased, pulmonary functions improved, the lung tissues expression level of inflammatory factor and the fibrotic indicator were decreased, and the histopathological results showed the reduction of thickening of the inter-alveolar septa.

Conclusions: The Antrodia cinnamomea extract significant protects mice against bleomycin-induced lung injuries through improvement of body weight gain and lung functions, and attenuation of expression of inflammatory and fibrotic indicators.

Keywords: Antrodia cinnamomea; Bleomycin-induced pulmonary fibrosis; mTOR.