title: Hepatoprotective effects and antioxidant, antityrosinase activities of phloretin and phloretin isonicotinyl hydrazone.
abstract: BACKGROUND
  Acute liver damage is primarily induced by one of several causes, among them viral exposure, alcohol consumption, and drug and immune system issues. Agents with the ability to inhibit tyrosinase and protect against DNA damage caused by reactive oxygen species (ROS) may be therapeutically useful for the prevention or treatment of ROS-related diseases.
  
  
  METHODS
  This investigation examined the hepatoprotective effects of phloretin and phloretin isonicotinyl hydrazone (PIH) on d-galactosamine (D-GalN)-induced acute liver damage in Kunming mice, as well as the possible mechanisms. The serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyl transferase (γ-GT), alkaline phosphatase (ALP), and total bilirubin (TB) as well as the histopathological changes in mouse liver sections were determined. The antioxidant effects of phloretin, quercetin, and PIH on lipid peroxidation in rat liver mitochondria in vitro, 1,1-diphenyl-2-picrylhydrazyl (DPPH) or 2,2-azino-bis-(3-ethylbenzthiazoline-6-sulphonic acid) (ABTS) free radical scavenging activity in vitro, and supercoiled pBR322 plasmid DNA were confirmed. The experiment also examined the antityrosinase activity, inhibition type, and inhibition constant of phloretin and PIH.
  
  
  RESULTS
  Phloretin, quercetin, or PIH significantly prevented the increase in serum ALT, AST, γ-GT, ALP, and TB in acute liver damage induced by D-GalN, and produced a marked reduction in the histopathological hepatic lesions. Phloretin, quercetin, or PIH also exhibited antioxidant effects on lipid peroxidation in rat liver mitochondria in vitro, DPPH or ABTS free radical scavenging activity in vitro, and supercoiled pBR322 plasmid DNA. Phloretin, quercetin, or PIH also exhibited good antityrosinase activity.
  
  
  CONCLUSIONS
  To the best of our knowledge, this was the first study of the hepatoprotective effects of phloretin and PIH on D-GalN-induced acute liver damage in Kunming mice as well as the possible mechanisms. This was also the first study of the lipid peroxidation inhibition activity of phloretin and PIH in liver mitochondria induced by the Fe(2+)/vitamin C (Vc) system in vitro, the protective effects on supercoiled pBR322 plasmid DNA, and the antityrosinase activity of phloretin and PIH.
authors.affiliation: State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang, Jiangxi, China; Jiangxi University of Traditional Chinese Medicine, Nanchang, Jiangxi, China.
authors.forename: Ai-Ren
authors.initials: AR
authors.lastname: Zuo
authors.affiliation: Department of Chemistry, Nanchang University, Nanchang, Jiangxi, China.
authors.forename: Yan-Ying
authors.initials: YY
authors.lastname: Yu
authors.affiliation: Jiangxi University of Traditional Chinese Medicine, Nanchang, Jiangxi, China.
authors.forename: Qing-Long
authors.initials: QL
authors.lastname: Shu
authors.affiliation: Jiangxi University of Traditional Chinese Medicine, Nanchang, Jiangxi, China.
authors.forename: Li-Xiang
authors.initials: LX
authors.lastname: Zheng
authors.affiliation: Jiangxi University of Traditional Chinese Medicine, Nanchang, Jiangxi, China.
authors.forename: Xiao-Min
authors.initials: XM
authors.lastname: Wang
authors.affiliation: Jiangxi University of Traditional Chinese Medicine, Nanchang, Jiangxi, China.
authors.forename: Shu-Hong
authors.initials: SH
authors.lastname: Peng
authors.affiliation: Jiangxi University of Traditional Chinese Medicine, Nanchang, Jiangxi, China.
authors.forename: Yan-Fei
authors.initials: YF
authors.lastname: Xie
authors.affiliation: State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang, Jiangxi, China; Department of Chemistry, Nanchang University, Nanchang, Jiangxi, China. Electronic address: yuyanying@ncu.edu.cn.
authors.forename: Shu-Wen
authors.initials: SW
authors.lastname: Cao
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood / Q000473:pathology / Q000517:prevention & control*; D005260:Female; D008297:Male; D051379:Mice; D014442:Monophenol Monooxygenase / Q000037:antagonists & inhibitors*; D010693:Phloretin / Q000031:analogs & derivatives / Q000494:pharmacology* / Q000627:therapeutic use*; D051381:Rats
chemical_list: D000975:Antioxidants; C000603415:phloretin isonicotinyl hydrazone; D014442:Monophenol Monooxygenase; D010693:Phloretin
keywords: acute liver damage; antioxidant activity; antityrosinase activity; d-galactosamine; phloretin; phloretin isonicotinyl hydrazone