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Int Immunopharmacol. 2019 Mar;68:171-178. doi: 10.1016/j.intimp.2018.12.059. Epub 2019 Jan 11.

Hepatoprotective effects and structure-activity relationship of five flavonoids against lipopolysaccharide/d-galactosamine induced acute liver failure in mice.

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College of Pharmaceutical Sciences, Southwest University, Chongqing 400716, PR China.
West China Hospital, Sichuan University, Sichuan 610041, PR China.
Quality and Safety Center of Chongqing Agricultural Products, Chongqing 400020, PR China.
College of Life Science, Southwest University, Chongqing 400715, PR China.
College of Pharmaceutical Sciences, Southwest University, Chongqing 400716, PR China. Electronic address:


Acute liver failure (ALF) is a distinct clinical syndrome with high mortality and characterized by metabolic derangements, neurological complication, and multiple failures. Flavonoids exert great biological properties on anti-oxidation, anti-inflammation, and anti-apoptosis. After lipopolysaccharide (LPS)/d-galactosamine (d-GalN) administration, five flavonoids inhibited oxidative activities with reducing nitric oxide synthase (iNOS), malondialdehyde (MDA), and improving catalase (CAT), superoxide dismutase (SOD), total antioxidant capacity (T-AOC), nuclear factor erythroid-derived 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1). They reduced the serum levels of alanine and aspartate aminotransferase (ALT, AST) and pro-inflammatory cytokines, prevented the phosphorylation of IKK, IκBα, and NF-κB/p65 in the NF-κB signaling pathway. Additionally five flavonoids inhibited hepatocyte apoptosis through increasing Bcl-2/Bax ratio and suppressing the Caspase family proteins. Chrysin, luteolin, apigenin, hesperetin and 3', 4'-dimethoxy hesperetin have apparently hepato-protective effects against ALF induced by LPS/d-GalN. The study found, the C2C3 double bond at A ring, and the hydroxyl group of C3' or C4' at B ring increased the protective activities, however, the effect of hydroxymethylation at C3' and C4' was reversed. In addition, apigenin has good hepatoprotective effects and potential as a promising therapeutic agent for ALF in clinical application.


Acute liver failure; Anti-apoptosis; Anti-inflammation; Flavonoids; Oxidative stress

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