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Berberine ameliorates lipopolysaccharide‐induced acute lung injury via the PERK ‐mediated Nrf2/HO‐1 signaling axis
Author(s) -
Liang Yuan,
Fan Chongxi,
Yan Xiaolong,
Lu Xi,
Jiang Hua,
Di Shouyin,
Ma Zhiqiang,
Feng Yingtong,
Zhang Zhengbin,
Feng Pan,
Feng Xiao,
Feng Jianyu,
Jin Faguang
Publication year - 2019
Publication title -
phytotherapy research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.019
H-Index - 129
eISSN - 1099-1573
pISSN - 0951-418X
DOI - 10.1002/ptr.6206
Subject(s) - berberine , unfolded protein response , pharmacology , thapsigargin , lipopolysaccharide , oxidative stress , phosphorylation , signal transduction , chemistry , p38 mitogen activated protein kinases , endoplasmic reticulum , microbiology and biotechnology , medicine , immunology , protein kinase a , biology , biochemistry
A fundamental element of acute lung injury (ALI) is the inflammatory response, which can affect the entire respiratory system, including the respiratory tract and alveoli. Berberine has gained attention because of its anti‐inflammatory effects. Nuclear factor‐erythroid 2‐related factor 2 (Nrf2) and endoplasmic reticulum (ER) stress are involved in lung injury. Nrf2 also acts as a protein kinase‐like ER kinase (PERK) substrate in heart disease. Therefore, this study investigated the effect of berberine against lipopolysaccharide (LPS)‐induced ALI and the role of the PERK‐mediated Nrf2/HO‐1 signaling axis. Berberine promoted Nrf2 nuclear translocation and phosphorylation in vitro. After LPS stimulation, this effect was further enhanced, whereas inflammatory factor (IL‐6 and IL‐8) release and reactive oxygen species generation were significantly decreased. Berberine effectively alleviated lung injury by reducing lung edema and neutrophil infiltration. Berberine also significantly reduced histopathological inflammatory changes via inhibition of ER stress and activation of Nrf2 signaling. Thapsigargin‐induced ER stress and small interference RNA (siRNA)‐mediated Nrf2 inhibition abrogated the protective effects of berberine in vitro, whereas siRNA‐mediated suppression of ER stress and sulforaphane‐induced Nrf2 activation further improved those effects. Importantly, ER stress induction led to Nrf2 activation, whereas PERK depletion partly reduced the level of Nrf2 phosphorylation and translocation in LPS‐induced cells. Therefore, berberine inhibits LPS‐induced ALI through the PERK‐mediated Nrf2/HO‐1 signaling axis.