Protective Effect of Fluorofenidone Against Acute Lung Injury Through Suppressing the MAPK/NF-κB Pathway

• Published in: Frontiers in pharmacology Vol. 12; p. 772031
• Main Authors: Lv, Xin, Yao, Tingting, He, Rongling, He, Yijun, Li, Mengyu, Han, Yuanyuan, Zhang, Yan, Long, Lingzhi, Jiang, Guoliang, Cheng, Xiaoyun, Xie, Yanyun, Huang, Ling, Peng, Zhangzhe, Hu, Gaoyun, Li, Qianbin, Tao, Lijian, Meng, Jie
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 20-12-2021
• Subjects: acute lung injury; apoptosis; fluorofenidone; inflammation; lipopolysaccharide; Pharmacology; fluorofenidone; apoptosis; lipopolysaccharide; inflammation; acute lung injury
• ISSN: 1663-9812; 1663-9812
• DOI: 10.3389/fphar.2021.772031

Acute lung injury (ALI) is a severe disease that presents serious damage and excessive inflammation in lungs with high mortality without effective pharmacological therapy. Fluorofenidone (AKFPD) is a novel pyridone agent that has anti-fibrosis, anti-inflammation, and other pharmacological activities, while the effect of fluorofenidone on ALI is unclarified. Here, we elucidated the protective effects and underlying mechanism of fluorofenidone on lipopolysaccharide (LPS)-induced ALI. In this study, fluorofenidone alleviated lung tissue structure injury and reduced mortality, decreased the pulmonary inflammatory cell accumulation and level of inflammatory cytokines IL-1β, IL-6, and TNF-α in the bronchoalveolar lavage fluid, and attenuated pulmonary apoptosis in LPS-induced ALI mice. Moreover, fluorofenidone could block LPS-activated phosphorylation of ERK, JNK, and P38 and further inhibited the phosphorylation of IκB and P65. These results suggested that fluorofenidone can significantly contrast LPS-induced ALI through suppressing the activation of the MAPK/NF-κB signaling pathway, which indicates that fluorofenidone could be considered as a novel therapeutic candidate for ALI.