10.1021/np2003935.s001 Woo-Cheol Lee Woo-Cheol Lee Hyun Ah Jung Hyun Ah Jung Jae Sue Choi Jae Sue Choi Yeong Shik Kim Yeong Shik Kim Sun-Mee Lee Sun-Mee Lee Protective Effects of Luteolin against Apoptotic Liver Damage Induced by d-Galactosamine/Lipopolysaccharide in Mice American Chemical Society 2011 serum level cytochrome c protein expression BH LPS Cirsium japonicum intraperitoneal injection GalN apoptotic pathways Apoptotic Liver Damage Induced Protective Effects TNF 1 attenuated apoptosis 1. Treatment protein expression serum aminotransferase activity 2011-09-23 00:00:00 Journal contribution https://acs.figshare.com/articles/journal_contribution/Protective_Effects_of_Luteolin_against_Apoptotic_Liver_Damage_Induced_by_d_Galactosamine_Lipopolysaccharide_in_Mice/2611684 In this study, the protective effects of luteolin (<b>1</b>, a major component of <i>Cirsium japonicum</i>) were examined against d-galactosamine (GalN)/lipopolysaccharide (LPS)-induced fulminant hepatic failure. Mice received an intraperitoneal injection of <b>1</b> (25, 50, 100, and 200 mg<b>·</b>kg<sup>–1</sup>) 1 h before treatment with GalN (700 mg<b>·</b>kg<sup>–1</sup>)/LPS (10 μg<b>·</b>kg<sup>–1</sup>). Treatment with GalN/LPS resulted in increased mortality and serum aminotransferase activity. These increases were attenuated by pretreatment with <b>1</b>. Treatment with GalN/LPS induced an increase in the serum level of tumor necrosis factor-α (TNF-α) and protein expression of TNF-α receptor-associated death domain, and these increases were prevented by <b>1</b>. In addition, <b>1</b> 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 <i>c</i> 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 <b>1</b>. 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.