Protective effect of baicalein against endotoxic shock in rats in vivo and in vitro
- 作者：Pao-Yun Cheng ; Yen-Mei Lee ; Yuan-Sheng Wu ; Tz-Wei Chang ; Jong-Shiaw Jin ; Mao-Hsiung Yen
- 关键词：Sepsis ; Reactive oxygen species ; Circulatory failure ; Nitric oxide ; NF-κ ; B ; Baicalein
- 刊名：Biochemical Pharmacology
- 出版年：2007
- 期刊代码：2_00062952
- 类别：pha
- 出版时间：15 March 2007
- 卷：73
- 期：6
- 页码：793-804
- 文件大小：1433 K
摘要
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 α (TNF-α). 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 6 h 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 IκBα, the formation of a nuclear factor kappa B (NF-κB)-DNA complex and NF-κB-dependent reporter gene expression. Thus, the therapeutic effects of baicalein were associated with reductions in TNF-α and superoxide anion levels during sepsis. The inhibitory effects of baicalein on iNOS production may be mediated by inhibition of the activation of NF-κB. Baicalein may thus prove a potential agent against endotoxemia.