Antimutagenic constituents from Monanthotaxis caffra (Sond.) Verdc

J Pharm Pharmacol. 2018 Jul;70(7):976-984. doi: 10.1111/jphp.12918. Epub 2018 Apr 6.

Abstract

Objectives: Monanthotaxis caffra (Sond.) Verdc. (Annonaceae) has been reported to possess antitumoural properties. Preliminary screening showed that the crude methanolic leaf extract had strong antimutagenic effects against aflatoxin B1 -induced mutagenicity. The aim of this study was to isolate and evaluate the antimutagenic properties of the active constituents from M. caffra.

Methods: Different chromatographic, spectroscopic and spectrometric techniques were used for the isolation and identification of the antimutagenic constituents. The antimutagenic effect of the extract and compounds was evaluated using Ames, Vitotox and Comet assays.

Key findings: Bioassay-guided fractionation of the methanolic leaf extract yielded two antimutagenic compounds identified as (+)-crotepoxide and 5,6-diacetoxy1-benzoyloxymethyl-1,3-cyclohexadiene. Crotepoxide had strong antimutagenicity in the Vitotox assay with an IC50 value of 131 μg/ml. 5,6-Diacetoxy-1-benzoyloxymethyl-1,3-cyclohexadiene showed strong antimutagenic activity in the Ames assay with an IC50 value of 348.9 μg/plate and no antimutagenic activity in the Vitotox test. Furthermore, the compound was able to inhibit, block or prevent biotransformation of aflatoxin B1 by repressing the proteins involved in transcription.

Conclusions: Crotepoxide and 5,6-diacetoxy-1-benzoyloxymethyl-1,3-cyclohexadiene have the potential to mitigate the risks arising from consumption of aflatoxin B1 -contaminated food and feed.

Keywords: (+)-crotepoxide; Monanthotaxis caffra; 5,6-diacetoxy-1-benzoyloxymethyl-1,3-cyclohexadiene; aflatoxin B1; antimutagenicity.

MeSH terms

  • Aflatoxin B1 / adverse effects
  • Aflatoxin B1 / antagonists & inhibitors
  • Annonaceae / chemistry*
  • Antimutagenic Agents / pharmacology*
  • Biotransformation / drug effects
  • Cyclohexenes / pharmacology*
  • Dose-Response Relationship, Drug
  • Epoxy Compounds / isolation & purification
  • Epoxy Compounds / pharmacology*
  • Humans
  • Molecular Structure
  • Mutagenicity Tests
  • Plant Extracts / chemistry
  • Plant Extracts / pharmacology*
  • Plant Leaves / chemistry
  • Tumor Cells, Cultured

Substances

  • 5,6-diacetoxy1-benzoyloxymethyl-1,3-cyclohexadiene
  • Antimutagenic Agents
  • Cyclohexenes
  • Epoxy Compounds
  • Plant Extracts
  • futoxide
  • Aflatoxin B1