Cheng Pao-Yun, Lee Yen-Mei, Wu Yuan-Sheng, Chang Tz-Wei, Jin Jong-Shiaw, Yen Mao-Hsiung
Department of Pharmacology, National Defense Medical Center, P.O. Box 90048-504, Nei-Hu 114, Taipei, Taiwan.
Biochem Pharmacol. 2007 Mar 15;73(6):793-804. doi: 10.1016/j.bcp.2006.11.025. Epub 2006 Dec 2.
Dried roots of Scutellaria baicalensis Georgi (Huang qin) are widely used in traditional Chinese medicine. Baicalein is a major bioactive flavonoid component of H. qin that shows a wide range of biological activities, including antioxidant and anti-inflammatory actions. We evaluated therapeutic effects and possible mechanisms of action of baicalein on circulatory failure and vascular dysfunction during sepsis induced by lipopolysaccharide (LPS; 10 mg/kg, i.v.) in anesthetized rats. Treatment of the rats with baicalein (20 mg/kg, i.v.) significantly attenuated the deleterious hemodynamic changes of hypotension and tachycardia caused by LPS and significantly inhibited the elevation of plasma tumor necrosis factor alpha (TNF-alpha). Baicalein also decreased levels of inducible nitric oxide synthase (iNOS) and the overproduction of NO and superoxide anions caused by LPS. It also increased the survival rate of ICR mice (25-30 g) challenged by LPS (60 mg/kg). Moreover, infiltration of neutrophils into the liver and lungs of rats 6h after treatment with LPS was also reduced by baicalein. To investigate the mechanism of action of baicalein on sepsis, RAW 264.7 cells were used as a model. Baicalein inhibited iNOS protein production, and suppressed LPS-induced degradation of IkappaBalpha, the formation of a nuclear factor kappa B (NF-kappaB)-DNA complex and NF-kappaB-dependent reporter gene expression. Thus, the therapeutic effects of baicalein were associated with reductions in TNF-alpha and superoxide anion levels during sepsis. The inhibitory effects of baicalein on iNOS production may be mediated by inhibition of the activation of NF-kappaB. Baicalein may thus prove a potential agent against endotoxemia.
黄芩（Huang qin）的干燥根在传统中药中广泛应用。黄芩苷是黄芩的主要生物活性黄酮类成分，具有广泛的生物活性，包括抗氧化和抗炎作用。我们评估了黄芩苷对脂多糖（LPS；10 mg/kg，静脉注射）诱导的麻醉大鼠脓毒症期间循环衰竭和血管功能障碍的治疗效果及可能的作用机制。用黄芩苷（20 mg/kg，静脉注射）治疗大鼠可显著减轻LPS引起的低血压和心动过速等有害血流动力学变化，并显著抑制血浆肿瘤坏死因子α（TNF-α）的升高。黄芩苷还可降低诱导型一氧化氮合酶（iNOS）水平以及LPS引起的NO和超氧阴离子的过量产生。它还提高了受LPS（60 mg/kg）攻击的ICR小鼠（25 - 30 g）的存活率。此外，黄芩苷还减少了LPS治疗6小时后大鼠肝脏和肺中中性粒细胞浸润。为了研究黄芩苷对脓毒症的作用机制，以RAW 264.7细胞为模型。黄芩苷抑制iNOS蛋白产生，并抑制LPS诱导的IkappaBalpha降解、核因子kappa B（NF-kappaB）-DNA复合物形成以及NF-kappaB依赖性报告基因表达。因此，黄芩苷的治疗效果与脓毒症期间TNF-α和超氧阴离子水平降低有关。黄芩苷对iNOS产生的抑制作用可能是通过抑制NF-kappaB的激活介导的。因此，黄芩苷可能是一种潜在的抗内毒素血症药物。
