Protective effect of baicalein against endotoxic shock in rats in vivo and in vitro.
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.
Cheng
Pao-Yun
PY
Department of Pharmacology, National Defense Medical Center, P.O. Box 90048-504, Nei-Hu 114, Taipei, Taiwan.
Lee
Yen-Mei
YM
Wu
Yuan-Sheng
YS
Chang
Tz-Wei
TW
Jin
Jong-Shiaw
JS
Yen
Mao-Hsiung
MH
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis; D019446:Endotoxemia / Q000188:drug therapy / Q000503:physiopathology; D044950:Flavanones / Q000627:therapeutic use*; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D020556:Neutrophil Infiltration / Q000187:drug effects; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D011921:Rats, Inbred WKY; D012772:Shock, Septic / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D013481:Superoxides / Q000378:metabolism; D014661:Vasoconstriction / Q000187:drug effects
D016207:Cytokines; D044950:Flavanones; D016328:NF-kappa B; D013481:Superoxides; C006680:baicalein; D009638:Norepinephrine