Antiproliferative and toxicological properties of drimanes obtained from Drimys brasiliensis stem barks

Biomed Pharmacother. 2018 Jul;103:1498-1506. doi: 10.1016/j.biopha.2018.04.103. Epub 2018 May 7.

Abstract

Stem barks of Drimys brasiliensis (Winteraceae) are consumed by the population in the form of a condiment. It is widely used to treat gastric and stomach problems and also to treat cancer. The extracts have demonstrated antiproliferative, antileishmanial and antimicrobial activities assigned to drimane sesquiterpenes. This study aimed to optimize the extraction conditions of the drimanes sesquiterpenes identified as 1-β-(p-coumaroyloxy)-polygodial 1, drimanial 2 and 1-β-(p-methoxycinnamoyl)-polygodial 3 in stem bark extracts. The HPLC-DAD method was developed and validated for the quantification of drimanes 1-3. The cytotoxic activity of these drimanes in human cancer cells, and the toxicological effects of the hydroethanolic extract, were determined. The extracts were prepared using different extractive conditions (solvents, plant: solvent ratio and time). The cytotoxicity effect was evaluated against leukemia, lymphomas, carcinomas and sarcomas cells using the tetrazolium assay (MTT). Furthermore, the acute toxicity was determined by measuring the biochemical parameters and by histopathological analysis. The hemolytic activity and micronucleus test were also performed. The method was linear, sensitive, precise and accurate for both drimanes 1-3. The best condition for extraction was using dichloromethane with plant: solvent proportion 1:10 (w/v) for six hours under dynamic maceration. Isolated drimanes exhibited cytotoxic effects with IC50 values ​​ranging from 0.13 to 112.67 μM. Compound 1 demonstrated significant results for acute promyelocytic leukemia (NB4) and Burkitt's lymphoma (RAMOS) cells while driamane 3 for Burkitt's lymphoma (RAJI) and acute T cell leukemia (MOLT4) cells. No signs of toxicity was observed and neither was mutagenicity or hemolytic activity.

Keywords: Cytotoxicity; Drimanes sesquiterpenes; Drimys brasiliensis; HPLC; Toxicology.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Drimys / chemistry*
  • Ethanol / chemistry
  • Hemolysis / drug effects
  • Humans
  • Limit of Detection
  • Micronucleus Tests
  • Organ Size / drug effects
  • Plant Bark / chemistry*
  • Plant Extracts / pharmacology
  • Plant Extracts / toxicity
  • Plant Stems / chemistry*
  • Polycyclic Sesquiterpenes
  • Rats, Wistar
  • Reproducibility of Results
  • Sesquiterpenes / chemistry
  • Sesquiterpenes / pharmacology*
  • Sesquiterpenes / toxicity*
  • Toxicity Tests, Acute*

Substances

  • Plant Extracts
  • Polycyclic Sesquiterpenes
  • Sesquiterpenes
  • drimane
  • Ethanol