Tan Zheng Huai, Yu Ling Hong, Wei Huai Lin, Liu Geng Tao
Department of Pharmacology, Institute of Materia Medica, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing 100050, China.
J Pharm Pharmacol. 2007 Jan;59(1):115-21. doi: 10.1211/jpp.59.1.0015.
Scutellarin is a natural compound from a Chinese herb. The purpose of this paper was to study the protective effect of scutellarin on concanavalin A (Con A)-induced immunological liver injury and its effect on liver nuclear factor kappaB (NF-kappaB), tumor necrosis factor alpha (TNF-alpha), interferon gamma (IFN-gamma), and inducible nitric oxide synthase (iNOS) expression in mice. Mouse liver injury was produced by injection of Con A 25 mg kg-1 via the tail vein. Scutellarin 50 or 100 mg kg-1 was peritoneally administered to mice 9 or 1 h before injection of Con A. The levels of serum alanine aminotransferase (ALT) and asparatate aminotransferase (AST), NO2-/NO3- and TNF-alpha were determined with biochemical kits, and ELISA using Quantikine Mouse TNF-alpha kit according the manufacturer's instructions. Liver lesions were examined by light microscope. The expression of TNF-alpha, IFN-gamma, iNOS and Fas mRNA in the livers was detected by RT-PCR; and the expression of c-Fos, c-Jun, iNOS and IkappaB proteins was measured by Western Blotting. As a result, pretreatment with scutellarin 100 mg kg-1 significantly decreased the serum ALT, AST, NO2-/NO3- and TNF-alpha levels, and also reduced liver lesions induced by Con A. Scutellarin 100 mg kg-1 down-regulated expression of TNF-alpha and iNOS mRNA, and c-Fos, c-Jun and iNOS protein, while scutellarin enhanced the degradation of IkappaB in the livers of mice injected with Con A. The results suggest that scutellarin has a protective action against Con A-induced liver injury in mice, and its active mechanism may be related to the inhibition of the NF-kappaB-TNF-alpha-iNOS transduction pathway.
灯盏花素是一种源自中草药的天然化合物。本文旨在研究灯盏花素对刀豆蛋白A（Con A）诱导的免疫性肝损伤的保护作用及其对小鼠肝细胞核因子κB（NF-κB）、肿瘤坏死因子α（TNF-α）、干扰素γ（IFN-γ）和诱导型一氧化氮合酶（iNOS）表达的影响。通过尾静脉注射25 mg/kg的Con A诱导小鼠肝损伤。在注射Con A前9或1小时，给小鼠腹腔注射50或100 mg/kg的灯盏花素。使用生化试剂盒测定血清丙氨酸氨基转移酶（ALT）和天冬氨酸氨基转移酶（AST）、NO2-/NO3-和TNF-α的水平，并根据制造商的说明使用Quantikine小鼠TNF-α试剂盒通过酶联免疫吸附测定法（ELISA）进行检测。通过光学显微镜检查肝脏病变。通过逆转录聚合酶链反应（RT-PCR）检测肝脏中TNF-α、IFN-γ、iNOS和Fas mRNA的表达；并通过蛋白质免疫印迹法（Western Blotting）测定c-Fos、c-Jun、iNOS和IkappaB蛋白的表达。结果显示，用100 mg/kg的灯盏花素预处理可显著降低血清ALT、AST、NO2-/NO3-和TNF-α水平，还可减轻Con A诱导的肝脏病变。100 mg/kg的灯盏花素下调TNF-α和iNOS mRNA以及c-Fos、c-Jun和iNOS蛋白的表达，而灯盏花素增强了注射Con A的小鼠肝脏中IkappaB的降解。结果表明，灯盏花素对Con A诱导的小鼠肝损伤具有保护作用，其作用机制可能与抑制NF-κB-TNF-α-iNOS信号转导通路有关。
