Formononetin attenuates cigarette smoke‐induced <scp>COPD</scp> in mice by suppressing inflammation, endoplasmic reticulum stress, and apoptosis in bronchial epithelial cells via <scp>AhR</scp>/<scp>CYP1A1</scp> and <scp>AKT</scp>/<scp>mTOR</scp> signaling pathways
Xiaomei Li, Xianhan Jiang, Runhao Zeng, Xiujuan Lai, Jing Wang, Hao Liu, Huihui Wu, HE Jia-xun, Lian Liu, Zhiying Zhu, Jingpei Li, Xue Liang
Abstract
Chronic obstructive pulmonary disease (COPD) is a chronic, progressive, and lethal lung disease with few treatments. Formononetin (FMN) is a clinical preparation extract with extensive pharmacological actions. However, its effect on COPD remains unknown. This study aimed to explore the effect and underlying mechanisms of FMN on COPD. A mouse model of COPD was established by exposure to cigarette smoke (CS) for 24 weeks. In addition, bronchial epithelial BEAS-2B cells were treated with CS extract (CSE) for 24 h to explore the in vitro effect of FMN. FMN significantly improved lung function and attenuated pathological lung damage. FMN treatment reduced inflammatory cell infiltration and pro-inflammatory cytokines secretion. FMN also suppressed apoptosis by regulating apoptosis-associated proteins. Moreover, FMN relieved CS-induced endoplasmic reticulum (ER) stress in the mouse lungs. In BEAS-2B cells, FMN treatment reduced CSE-induced inflammation, ER stress, and apoptosis. Mechanistically, FMN downregulated the CS-activated AhR/CYP1A1 and AKT/mTOR signaling pathways in vivo and in vitro. FMN can attenuate CS-induced COPD in mice by suppressing inflammation, ER stress, and apoptosis in bronchial epithelial cells via the inhibition of AhR/CYP1A1 and AKT/mTOR signaling pathways, suggesting a new therapeutic potential for COPD treatment.