Tsai Chen-Liang, Lin Yu-Chieh, Wang Hui-Min, Chou Tz-Chong
Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Tri-Service General Hospital, Taipei, Taiwan.
Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan.
J Ethnopharmacol. 2014 Apr 11;153(1):197-206. doi: 10.1016/j.jep.2014.02.010. Epub 2014 Feb 15.
Baicalein (BE), a phenolic flavonoid extracted mainly from the root of Scutellaria baicalensis Georgi, a Chinese herb, is traditionally used in oriental medicine. Several studies have demonstrated that BE exerts many beneficial effects including anti-inflammatory and antioxidant activities. However, its effect on acute lung injury (ALI) and the molecular mechanisms involved remain unclear and warrant further investigation. The aim of the study is to investigate whether BE improves lipopolysaccharide (LPS, intratracheally, i.t.)-induced ALI in rats, and further study the underlying mechanisms of its activity.
Rats were administrated with LPS (5mg/kg/body weight, i.t.) through a 24-gauge catheter to establish the ALI model. The effects of BE on the levels of pro-inflammatory cytokines, nitrite/nitrate in bronchoalveolar lavage fluid, and the expression of nuclear factor-erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1) and nuclear factor-kappa B (NF-κB) activation as well as the histopathological changes were evaluated.
Results showed that BE (20mg/kg, i.p.) treatment markedly attenuated LPS-induced lung edema, elevation of the levels of IL-1β, TNF-α, IL-6, CINC-3, and nitrite/nitrate in bronchoalveolar lavage fluid accompanied by a remarkable improvement of lung histopathological symptoms. The LPS-enhanced inflammatory cell infiltration and myeloperoxidase activity, O2(-) formation and the expression of inducible nitric oxide synthase and nitrotyrosin in lungs were all attenuated by BE. Notably, BE could augment Nrf2/HO-1 cascade, but inhibited NF-κB activation in LPS-instilled lungs that was strongly reversed by blocking HO-1 activity.
This study is the first to demonstrate that BE protects against LPS-induced ALI in rats. The underlying mechanisms may include inhibition of NF-κB-mediated inflammatory responses and upregulation of Nrf2/HO-1 pathway, which ultimately alleviates the pathological symptoms of ALI.
黄芩素（BE）是一种主要从中国草药黄芩的根部提取的酚类黄酮，传统上用于东方医学。多项研究表明，黄芩素具有多种有益作用，包括抗炎和抗氧化活性。然而，其对急性肺损伤（ALI）的影响及其涉及的分子机制仍不清楚，值得进一步研究。本研究的目的是探讨黄芩素是否能改善脂多糖（LPS，经气管内，i.t.）诱导的大鼠ALI，并进一步研究其活性的潜在机制。
通过24号导管给大鼠经气管内注射LPS（5mg/kg体重，i.t.）以建立ALI模型。评估黄芩素对促炎细胞因子水平、支气管肺泡灌洗液中亚硝酸盐/硝酸盐水平、核因子红细胞2相关因子2（Nrf2）、血红素加氧酶-1（HO-1）的表达以及核因子κB（NF-κB）激活的影响以及组织病理学变化。
结果表明，黄芩素（20mg/kg，腹腔注射）治疗显著减轻了LPS诱导的肺水肿、支气管肺泡灌洗液中IL-1β、TNF-α、IL-6、CINC-3水平以及亚硝酸盐/硝酸盐水平的升高，同时肺组织病理学症状有显著改善。LPS增强的肺组织炎症细胞浸润和髓过氧化物酶活性、O2（-）形成以及诱导型一氧化氮合酶和硝基酪氨酸的表达均被黄芩素减弱。值得注意的是，黄芩素可增强Nrf2/HO-1级联反应，但抑制LPS注入肺中的NF-κB激活，而通过阻断HO-1活性可强烈逆转这种抑制作用。
本研究首次证明黄芩素可保护大鼠免受LPS诱导的ALI。潜在机制可能包括抑制NF-κB介导的炎症反应和上调Nrf2/HO-1途径，最终减轻ALI的病理症状。
