Preclinical safety evaluation of the aqueous extract from Mangifera indica Linn. (Anacardiaceae): genotoxic, clastogenic and cytotoxic assessment in experimental models of genotoxicity in rats to predict potential human risks

J Ethnopharmacol. 2019 Oct 28:243:112086. doi: 10.1016/j.jep.2019.112086. Epub 2019 Jul 13.

Abstract

Ethnopharmacological relevance: Medicinal plants widely used by the population contain significant concentrations of biologically active compounds and, although they have proven pharmacological properties, can cause DNA damage and develop fatal diseases.

Aim of the study: The present study aimed to evaluate the genotoxic, cytotoxic potential and clastogenic effects of the aqueous extract from Mangifera indica leaves (EAMI) on rats submitted to experimental genotoxicity models and through the SMART test performed in Drosophila melanogaster.

Material and methods: The comet assay and the micronucleus test were performed on peripheral and bone marrow blood, respectively, of Wistar rats, orally treated with EAMI at doses of 125, 250, 500 and 1000 mg/kg/bw for 28 days. In the SMART test, the standard cross between three mutant D. melanogaster strains was used. Larvae were treated with EAMI at different concentrations, and the wings of adult flies were evaluated for the presence/frequency of mutant spots and compared to the negative control group.

Results: Phytochemical analysis of EAMI indicated high levels of flavonoids. The tests performed in rats showed that EAMI did not present significant genotoxic or clastogenic effects. The results showed a critical dose-dependent cytoprotective effect exerted by EAMI. This result was attributed to the high content of polyphenols and flavonoids. The biotransformation metabolites of EAMI did not present genotoxic activity, as demonstrated by the SMART test.

Conclusions: These results are relevant since they provide safety information about a plant species of great therapeutic, economical, nutritious and ethnopharmacological value for the population.

Keywords: Comet assay; Genotoxicity; Mangifera indica; Micronucleus; Mutagenesis; Preclinical safety; SMART test.

MeSH terms

  • Animals
  • Comet Assay
  • Drosophila melanogaster / drug effects
  • Drosophila melanogaster / genetics
  • Female
  • Flavonoids / analysis
  • Flavonoids / toxicity
  • Humans
  • Male
  • Mangifera*
  • Micronucleus Tests
  • Phytochemicals / analysis
  • Phytochemicals / toxicity
  • Plant Extracts / chemistry
  • Plant Extracts / toxicity*
  • Plant Leaves / classification
  • Rats, Wistar
  • Risk Assessment

Substances

  • Flavonoids
  • Phytochemicals
  • Plant Extracts