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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.

Author information

1
College of Pharmaceutical Sciences, Southwest University, Chongqing 400716, PR China.
2
West China Hospital, Sichuan University, Sichuan 610041, PR China.
3
Quality and Safety Center of Chongqing Agricultural Products, Chongqing 400020, PR China.
4
College of Life Science, Southwest University, Chongqing 400715, PR China.
5
College of Pharmaceutical Sciences, Southwest University, Chongqing 400716, PR China. Electronic address: zbs360@swu.edu.cn.

Abstract

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.

KEYWORDS:

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

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