Flavonoid constituents of Dobera glabra leaves: amelioration impact against CCl4-induced changes in the genetic materials in male rats

Pharm Biol. 2017 Dec;55(1):139-145. doi: 10.1080/13880209.2016.1230879. Epub 2016 Sep 23.

Abstract

Context: Dobera glabra (Forssk.) Poir (Salvadoraceae) is a highly valued tree with diverse importance as special mineral sourced feed and a folkloric tool for forecasting droughts. However, there are no reports on its phytochemical and biological investigations.

Objective: Phytochemical investigation of D. glabra leaves and its protective potential against CCl4 inducing changes in the genetic materials.

Materials and methods: D. glabra extract, DGE (70% MeOH/H2O), was applied to polyamide column chromatography, eluting with MeOH/H2O of decreasing polarities, followed by preparative chromatographic tools, yielded seven compounds. Three DGE doses (50, 100 and 200 mg/kg bw/d) were administrated for 8 weeks intragastrically to male albino rats prior treated with CCl4 (0.5 mL/kg/bw). The reactive oxygen species (ROS) levels, expression changes of glutamate transporters (GLAST, GLT-1 and SNAT3) mRNA, DNA fragmentation and glutathione peroxidase (GPx) activity were investigated in the liver tissues of these rats.

Results: Isorhamnetin-3-O-β-glucopyranoside-7-O-α-rhamnopyranoside, isorhamnetin-3-O-α-rhamnopyranoside-7-O-β-glucopyranoside, kaempferol-3,7-di-O-α-rhamnopyranoside, isorhamnetin-3-O-β-glucopyranoside, kaempferol-3-O-β-glucopyranoside, isorhamnetin and kaempferol were identified. DGE (200 mg/kg bw) + CCl4 exhibited the most significant reduction in ROS levels and DNA fragmentation with 251.3% and141% compared to 523.1% and 273.2% for CCl4, respectively. Additionally, it increased significantly the mRNA expression of GLAST, GLT-1 and SNAT3 to 2.16-, 1.72- and 2.09-fold, respectively. Also, GPx activity was increased to 4.8 U/mg protein/min compared to CCl4 (1.8 U/mg protein/min).

Discussion and conclusion: Flavonoid constituents, antioxidant effect and genotoxic protection activity of D. glabra were first reported. DGE may be valuable in the treatment and hindrance of hepatic oxidative stress and genotoxicity.

Keywords: DNA fragmentation; ROS; gene expression; glutathione peroxidase.

MeSH terms

  • Amino Acid Transport Systems, Neutral / genetics
  • Amino Acid Transport Systems, Neutral / metabolism
  • Animals
  • Antioxidants / isolation & purification
  • Antioxidants / pharmacology*
  • Carbon Tetrachloride*
  • Chemical and Drug Induced Liver Injury / genetics
  • Chemical and Drug Induced Liver Injury / metabolism
  • Chemical and Drug Induced Liver Injury / prevention & control*
  • DNA Damage / drug effects*
  • Disease Models, Animal
  • Excitatory Amino Acid Transporter 1 / genetics
  • Excitatory Amino Acid Transporter 1 / metabolism
  • Excitatory Amino Acid Transporter 2 / genetics
  • Excitatory Amino Acid Transporter 2 / metabolism
  • Flavonoids / isolation & purification
  • Flavonoids / pharmacology*
  • Glutathione Peroxidase / metabolism
  • Liver / drug effects*
  • Liver / metabolism
  • Male
  • Methanol / chemistry
  • Oxidative Stress / drug effects*
  • Phytotherapy
  • Plant Extracts / isolation & purification
  • Plant Extracts / pharmacology*
  • Plant Leaves / chemistry*
  • Plants, Medicinal
  • RNA, Messenger / metabolism
  • Rats
  • Reactive Oxygen Species / metabolism
  • Salvadoraceae / chemistry*
  • Solvents / chemistry
  • Up-Regulation

Substances

  • Amino Acid Transport Systems, Neutral
  • Antioxidants
  • Excitatory Amino Acid Transporter 1
  • Excitatory Amino Acid Transporter 2
  • Flavonoids
  • Plant Extracts
  • RNA, Messenger
  • Reactive Oxygen Species
  • Slc1a2 protein, rat
  • Slc1a3 protein, rat
  • Solvents
  • system N protein 1
  • Carbon Tetrachloride
  • Glutathione Peroxidase
  • Methanol