title: Afzelin ameliorates D-galactosamine and lipopolysaccharide-induced fulminant hepatic failure by modulating mitochondrial quality control and dynamics.
abstract: Fulminant hepatic failure (FHF) is a fatal clinical syndrome that results in excessive inflammation and hepatocyte death. Mitochondrial dysfunction is considered to be a possible mechanism of FHF. Afzelin, a flavonol glycoside found in Houttuynia cordata Thunberg, has anti-inflammatory and antioxidant properties. The present study elucidated the cytoprotective mechanisms of afzelin against D-galactosamine (GalN)/LPS induced FHF, particularly focusing on mitochondrial quality control and dynamics.
  
  
  
  Mice were administered afzelin i.p. 1 h before receiving GalN (800 mg·kg-1)/LPS (40 μg·kg-1), and they were then killed 5 h after GalN/LPS treatment.
  
  
  
  Afzelin improved the survival rate and reduced the serum levels of alanine aminotransferase and pro-inflammatory cytokines in GalN/LPS-treated mice. Afzelin attenuated the mitochondrial damage, as indicated by diminished mitochondrial swelling and mitochondrial glutamate dehydrogenase activity in GalN/LPS-treated mice. Afzelin enhanced mitochondrial biogenesis, as indicated by increased levels of PPAR-γ coactivator 1α, nuclear respiratory factor 1 and mitochondrial transcription factor A. Afzelin also decreased the level of mitophagy-related proteins, parkin and PTEN-induced putative kinase 1. Furthermore, while GalN/LPS significantly increased the level of fission-related protein, dynamin-related protein 1, and decreased the level of fusion-related protein, mitofusin 2; these effects were attenuated by afzelin.
  
  
  
  Our findings demonstrated that afzelin protects against GalN/LPS-induced liver injury by enhancing mitochondrial biogenesis, suppressing excessive mitophagy and balancing mitochondrial dynamics.
authors.affiliation: School of Pharmacy, Sungkyunkwan University, Suwon, South Korea.
authors.forename: Sang-Bin
authors.initials: SB
authors.lastname: Lee
authors.affiliation: School of Pharmacy, Sungkyunkwan University, Suwon, South Korea.
authors.forename: Jung-Woo
authors.initials: JW
authors.lastname: Kang
authors.affiliation: School of Pharmacy, Sungkyunkwan University, Suwon, South Korea.
authors.forename: So-Jin
authors.initials: SJ
authors.lastname: Kim
authors.affiliation: College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, South Korea.
authors.forename: Jongmin
authors.initials: J
authors.lastname: Ahn
authors.affiliation: College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, South Korea.
authors.forename: Jinwoong
authors.initials: J
authors.lastname: Kim
authors.affiliation: School of Pharmacy, Sungkyunkwan University, Suwon, South Korea.
authors.forename: Sun-Mee
authors.initials: SM
authors.lastname: Lee
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D005688:Galactosamine; D008070:Lipopolysaccharides; D017114:Liver Failure, Acute / Q000139:chemically induced* / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008362:Mannosides / Q000494:pharmacology*; D051379:Mice; D008813:Mice, Inbred ICR; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D044945:Proanthocyanidins / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D008070:Lipopolysaccharides; D008362:Mannosides; D044945:Proanthocyanidins; C477954:afzelin; D005688:Galactosamine