Protective Effects of Luteolin against Apoptotic Liver Damage Induced by D-Galactosamine/Lipopolysaccharide in Mice

作者：Lee Woo Cheol; Jung Hyun Ah; Choi Jae Sue; Kim Yeong Shik; Lee Sun Mee^*

来源：Journal of Natural Products, 2011, 74(9): 1916-1921.

DOI：10.1021/np2003935

In this study, the protective effects of luteolin (1, a major component of Cirsium japonicum) were examined against D-galactosamine (GalN)/lipopolysaccharide (LPS)-induced fulminant hepatic failure. Mice received an intraperitoneal injection of 1 (25, 50, 100, and 200 mg.kg(-1)) 1 h before treatment with GalN (700 mg.kg(-1))/LPS(10 mu g.kg(-1)). Treatment with GalN/LPS resulted in increased mortality and serum aminotransferase activity. These increases were attenuated by pretreatment with 1. Treatment with GalN/LPS induced an increase in the serum level of tumor necrosis factor-alpha (TNF-alpha) and protein expression of TNF-alpha receptor-associated death domain, and these increases were prevented by 1. In addition, 1 attenuated apoptosis induced by GalN /LPS treatment, which was analyzed using a caspase-3 and -8 activity assay, as well as by proapoptotic BH3-only protein and cytochrome c protein expression, and by a terminal deoxynuleotidyl transferase-mediated dUTP nick end-labeling method. After GalN/LPS injection, nuclear phosphorylated c-Jun levels showed a significant increase, which were attenuated by 1. The present findings suggest that luteolin ameliorates D-GalN/LPS-induced liver injury and that this protection is likely due to inhibition of the extrinsic and intrinsic apoptotic pathways.

• 出版日期2011-9