p62-Nrf2 Regulatory Loop Mediates the Anti-Pulmonary Fibrosis Effect of Bergenin

• Published in: Antioxidants Vol. 11; no. 2; p. 307
• Main Authors: Zeng, Qian, Zhou, Tingting, Zhao, Feiyan, Xiong, Dayan, He, Bin, Hua, Qingzhong, Lin, Miao, Deng, Lang, Sang, Xiaoxue, Xie, Weixi, Chen, Jia, Wang, Zun, Ren, Lu, Luo, Ziqiang, Huang, Xiaoting, Liu, Wei, Tang, Siyuan
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 03.02.2022; MDPI
• Subjects: Antioxidants; bergenin; Bleomycin; Drug dosages; Extracellular matrix; FDA approval; Fibroblasts; Fibrosis; idiopathic pulmonary fibrosis; Laboratory animals; Lung diseases; myofibroblast; nuclear factor erythroid 2-related factor 2; Oxidative stress; p62/SQSTM1; Phosphorylation; Pulmonary fibrosis; Respiratory function; United States > US; China; Israel; p62/SQSTM1; bergenin; idiopathic pulmonary fibrosis; myofibroblast; nuclear factor erythroid 2-related factor 2; oxidative stress
• ISSN: 2076-3921; 2076-3921
• DOI: 10.3390/antiox11020307

Idiopathic pulmonary fibrosis (IPF) can severely disrupt lung function, leading to fatal consequences, and there is currently a lack of specific therapeutic drugs. Bergenin is an isocoumarin compound with lots of biological functions including antioxidant activity. This study evaluated the potential beneficial effects of bergenin on pulmonary fibrosis and investigated the possible mechanisms. We found that bergenin alleviated bleomycin-induced pulmonary fibrosis by relieving oxidative stress, reducing the deposition of the extracellular matrix (ECM) and inhibiting the formation of myofibroblasts. Furthermore, we showed that bergenin could induce phosphorylation and expression of p62 and activation of Nrf2, Nrf2 was required for bergenin-induced p62 upregulation, and p62 knockdown reduced bergenin-induced Nrf2 activity. More importantly, knockdown of Nrf2 or p62 could abrogate the antioxidant activity of bergenin and the inhibition effect of bergenin on TGF-β-induced ECM deposition and myofibroblast differentiation. Thereby, a regulatory loop is formed between p62 and Nrf2, which is an important target for bergenin aimed at treating pulmonary fibrosis.