Wan Jing-Yuan, Gong Xia, Zhang Li, Li Hong-Zhong, Zhou Yu-Fan, Zhou Qi-Xin
Department of Pharmacology, Chongqing Medical University, Chongqing 400016, PR China.
Eur J Pharmacol. 2008 Jun 10;587(1-3):302-8. doi: 10.1016/j.ejphar.2008.02.081. Epub 2008 Mar 7.
Baicalin, a traditional anti-inflammatory drug, has been found to protect against liver injury in several experimental animal hepatitis models; however, the mechanisms underlying the hepatoprotective properties of baicalin are poorly understood. In the present study,we investigated the effects of baicalin on the acute liver injury in mice induced by Lipopolysaccharide/D-galactosamine (LPS/D-GalN). Baicalin (50, 150, and 300 mg/kg) was pretreated intraperitoneally (i.p.) at 2, 24, and 48 h respectively before LPS/D-GalN injected in mice. The mortality, hepatic tissue histology, hepatic tissue Tumor necrosis factor-alpha (TNF-alpha) and myeloperoxidase (MPO), plasma levels of TNF-alpha and alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were analyzed. Besides, western blotting analyses of nuclear factor kappa B (NF-kappaB) translocation and Heme oxygenase-1(HO-1) protein expression, as well as HO-1 activity were determined. The results showed that baicalin protected against LPS/D-GalN-induced liver injury, including dose-dependent alleviation of mortality and hepatic pathological damage, decrease of ALT/AST release and the rise of MPO. Baicalin reduced nuclear translocation of NF-kappa B, TNF-alpha mRNA and protein levels in hepatic tissues and plasma levels of TNF-alpha induced by LPS/D-GalN. Moreover, baicalin dose-dependently increased HO-1 protein expression and activity. Further, inhibition of HO-1 activity significantly reversed the protective effect of baicalin against LPS/D-GalN-induced liver injury. These results suggest that baicalin can effectively prevent LPS/D-GalN-induced liver injury by inhibition of NF-kappa B activity to reduce TNF-alpha production and the underlying mechanism may be related to up-regulation of HO-1 protein and activity.
黄芩苷是一种传统的抗炎药物，已发现在多种实验性动物肝炎模型中可预防肝损伤；然而，黄芩苷保肝特性的潜在机制尚不清楚。在本研究中，我们研究了黄芩苷对脂多糖/ D -半乳糖胺（LPS / D - GalN）诱导的小鼠急性肝损伤的影响。在向小鼠注射LPS / D - GalN之前，分别在2、24和48小时腹腔内（i.p.）预处理黄芩苷（50、150和300 mg / kg）。分析了死亡率、肝组织组织学、肝组织肿瘤坏死因子-α（TNF-α）和髓过氧化物酶（MPO）、血浆TNF-α水平以及丙氨酸转氨酶（ALT）和天冬氨酸转氨酶（AST）。此外，还进行了核因子κB（NF-κB）易位、血红素加氧酶-1（HO-1）蛋白表达以及HO-1活性的蛋白质印迹分析。结果表明，黄芩苷可预防LPS / D - GalN诱导的肝损伤，包括剂量依赖性地减轻死亡率和肝病理损伤、降低ALT / AST释放以及MPO升高。黄芩苷减少了LPS / D - GalN诱导的肝组织中NF-κB的核易位、TNF-α mRNA和蛋白水平以及血浆TNF-α水平。此外，黄芩苷剂量依赖性地增加HO-1蛋白表达和活性。进一步的研究表明，抑制HO-1活性可显著逆转黄芩苷对LPS / D - GalN诱导的肝损伤的保护作用。这些结果表明，黄芩苷可通过抑制NF-κB活性以减少TNF-α产生，从而有效预防LPS / D - GalN诱导的肝损伤，其潜在机制可能与上调HO-1蛋白和活性有关。
