Acute lung injury (ALI) is a life-threatening syndrome that is characterized by overwhelming
lung inflammation and increased microvascular permeability, which causes a high mortality worldwide. Here, we studied the protective effect of
tetrahydroberberrubine (THBru), a
berberine derivative, on a mouse model of
lipopolysaccharide (LPS)-induced
acute lung injury that was established in our previous studies. The results showed that a single
oral administration of THBru significantly decreased the
lung wet to dry weight (W/D) ratio at doses of 2, 10 and 50mg/kg administered 1h prior to LPS challenge (30mg/kg,
intravenous injection). Histopathological changes, such as
pulmonary edema, infiltration of inflammatory cells and coagulation, were also attenuated by THBru. In addition, THBru markedly decreased the total cell counts, total
protein and
nitrate/
nitrite content in bronchoalveolar lavage fluid (BALF), significantly decreased
tumor necrosis factor-α (TNF-α) and
nitrate/
nitrite content in the plasma, and reduced the
myeloperoxidase (MPO) activity in the lung tissues. Additionally, THBru (10μM) significantly decreased the content of TNF-α and
nitric oxide (NO) in LPS-induced THP-1 cells in vitro. Moreover, THBru significantly suppressed the activation of the MAPKs JNK and p38, AKT, and the NF-κB subunit p65 in LPS-induced THP-1 cells. These findings confirm that THBru attenuates LPS-induced
acute lung injury by inhibiting the release of inflammatory
cytokines and suppressing the activation of MAPKs, AKT, and NF-κB signaling pathways, which implicates it as a potential therapeutic agent for ALI or
sepsis.