Li Weifeng, Huang Huimin, Niu Xiaofeng, Fan Ting, Hu Hua, Li Yongmei, Yao Huan, Li Huani, Mu Qingli
School of Pharmacy, Xi'an Jiaotong University, Number 76 Western Yanta Road, Xi'an City, Shaanxi, 710061, China,
Inflammation. 2014 Dec;37(6):2106-15. doi: 10.1007/s10753-014-9945-7.
Recent studies show that nuclear factor-kappa B (NF-κB) signaling pathway plays a key role in contributing to the development of lipopolysaccharide (LPS)-induced acute lung injury (ALI). Tetrahydrocoptisine is one of the main active components of Chelidonium majus L. and has been described to be effective in suppressing inflammation. The aim of the present study is to evaluate the protective effect of tetrahydrocoptisine on LPS-induced ALI in rats and clarify its underlying mechanisms of action. We found that in vivo pretreatment with tetrahydrocoptisine to rats 30 min before inducing ALI by LPS markedly decreased the mortality rate, lung wet weight to dry weight ratio, and ameliorated lung pathological changes. Meanwhile, tetrahydrocoptisine significantly inhibited the increase of the amounts of inflammatory cells, total protein content, tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) secretion in the bronchoalveolar lavage fluids (BALFs). Furthermore, tetrahydrocoptisine inhibited myeloperoxidase (MPO) accumulation in lung tissue and alleviated TNF-α and IL-6 production in serum. Additionally, immunohistochemistry showed that tetrahydrocoptisine efficiently reduced nuclear factor-kappa B (NF-κB) activation by inhibiting the translocation of NF-κBp65. In conclusion, our results demonstrate that tetrahydrocoptisine possesses a protective effect on LPS-induced ALI through inhibiting of NF-κB signaling pathways, which may involve the inhibition of pulmonary inflammatory process.
近期研究表明，核因子-κB（NF-κB）信号通路在脂多糖（LPS）诱导的急性肺损伤（ALI）发生发展过程中起关键作用。四氢黄连碱是白屈菜的主要活性成分之一，已被证实具有抗炎作用。本研究旨在评估四氢黄连碱对LPS诱导的大鼠ALI的保护作用，并阐明其潜在作用机制。我们发现，在通过LPS诱导ALI前30分钟对大鼠进行四氢黄连碱预处理，可显著降低死亡率、肺湿重与干重之比，并改善肺部病理变化。同时，四氢黄连碱可显著抑制支气管肺泡灌洗液（BALF）中炎症细胞数量增加、总蛋白含量升高、肿瘤坏死因子-α（TNF-α）和白细胞介素-6（IL-6）分泌。此外，四氢黄连碱可抑制肺组织中髓过氧化物酶（MPO）蓄积，并减轻血清中TNF-α和IL-6生成。另外，免疫组化显示，四氢黄连碱通过抑制NF-κBp65的易位有效降低核因子-κB（NF-κB）的激活。总之，我们的结果表明，四氢黄连碱通过抑制NF-κB信号通路对LPS诱导的ALI具有保护作用，这可能涉及对肺部炎症过程的抑制。
