Yao Jing, Pan Di, Zhao Yue, Zhao Li, Sun Jie, Wang Yu, You Qi-Dong, Xi Tao, Guo Qing-Long, Lu Na
Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, Nanjing, China; School of Life Science and Technology, China Pharmaceutical University, Nanjing, China.
Immunology. 2014 Oct;143(2):241-57. doi: 10.1111/imm.12305.
Acute lung injury (ALI) from a variety of clinical disorders, characterized by diffuse inflammation, is a cause of acute respiratory failure that develops in patients of all ages. Previous studies reported that wogonin, a flavonoid-like chemical compound which was found in Scutellaria baicalensis, has anti-inflammatory effects in several inflammation models, but not in ALI. Here, the in vivo protective effect of wogonin in the amelioration of lipopolysaccharide (LPS) -induced lung injury and inflammation was assessed. In addition, the in vitro effects and mechanisms of wogonin were studied in the mouse macrophage cell lines Ana-1 and RAW264.7. In vivo results indicated that wogonin attenuated LPS-induced histological alterations. Peripheral blood leucocytes decreased in the LPS-induced group, which was ameliorated by wogonin. In addition, wogonin inhibited the production of several inflammatory cytokines, including tumour necrosis factor-α, interleukin-1β (IL-1β) and IL-6, in the bronchoalveolar lavage fluid and lung tissues after LPS challenge, while the peroxisome proliferator-activated receptor γ (PPARγ) inhibitor GW9662 reversed these effects. In vitro results indicated that wogonin significantly decreased the secretion of IL-6, IL-1β and tumour necrosis factor-α in Ana-1 and RAW264.7 cells, which was suppressed by transfection of PPARγ small interfering RNA and GW9662 treatment. Moreover, wogonin activated PPARγ, induced PPARγ-mediated attenuation of the nuclear translocation and the DNA-binding activity of nuclear factor-κB in vivo and in vitro. In conclusion, all of these results showed that wogonin may serve as a promising agent for the attenuation of ALI-associated inflammation and pathology by regulating the PPARγ-involved nuclear factor-κB pathway.
各种临床病症引发的急性肺损伤（ALI）以弥漫性炎症为特征，是各年龄段患者急性呼吸衰竭的一个病因。先前的研究报道，汉黄芩素是一种在黄芩中发现的类黄酮化合物，在多种炎症模型中具有抗炎作用，但在ALI中却没有。在此，评估了汉黄芩素对改善脂多糖（LPS）诱导的肺损伤和炎症的体内保护作用。此外，还在小鼠巨噬细胞系Ana-1和RAW264.7中研究了汉黄芩素的体外作用及机制。体内结果表明，汉黄芩素减轻了LPS诱导的组织学改变。LPS诱导组外周血白细胞减少，而汉黄芩素改善了这一情况。此外，LPS攻击后，汉黄芩素抑制了支气管肺泡灌洗液和肺组织中包括肿瘤坏死因子-α、白细胞介素-1β（IL-1β）和IL-6在内的多种炎性细胞因子的产生，而过氧化物酶体增殖物激活受体γ（PPARγ）抑制剂GW9662逆转了这些作用。体外结果表明，汉黄芩素显著降低了Ana-1和RAW264.7细胞中IL-6、IL-1β和肿瘤坏死因子-α的分泌，而PPARγ小干扰RNA转染和GW9662处理抑制了这种分泌。此外，汉黄芩素激活了PPARγ，在体内和体外均诱导了PPARγ介导的核因子-κB核转位和DNA结合活性的减弱。总之，所有这些结果表明，汉黄芩素可能通过调节涉及PPARγ的核因子-κB途径，成为减轻ALI相关炎症和病理状况的一种有前景的药物。
