Toxicological, chemopreventive, and cytotoxic potentialities of rare vegetal species and supporting findings for the Brazilian Unified Health System (SUS)

ABSTRACT

Caatinga flora which are found in a poor Brazilian region contain a substantial number of endemic taxa with biomedical and social importance for regional communities. This study examined the antioxidant and cytotoxic potential of 35 samples (extracts/fractions) from 12 Caatinga species and determined the antiproliferative and genotoxic action of dichloromethane fraction from Mimosa caesalpiniifolia stem bark (DC-Mca) on human and vegetal cells. Samples were assessed for chemopreventive ability, toxic effects on Artemia salina shrimp as well as cytotoxicity on tumor cell lines and erythrocytes. DC-Mca was also tested with respect to antiproliferative and genotoxic effects upon normal leukocytes and meristematic cells from A. cepa roots. Some extracts reduced free radical levels >95% and 7 samples exhibited a lethal concentration (LC) ₅₀ < 100 µg/ml upon Artemia salina larvae. Eight samples displayed in vitro antitumor effects and three produced hemolysis. Data also demonstrated the pharmacological significance of bioactive extracts from Brazilian semi-arid region. There was no significant relationship between antioxidant, toxic, and antiproliferative activities, and that these properties were dependent upon the extractant. DC-Mca contained betulinic acid as main compound (approximately 70%), which showed higher (1) cytotoxic activity on cancer cell lines and dividing leukocytes, (2) reduced mitotic index of Allium cepa roots, and (3) induced cell cycle arrest and chromosomal bridges, thereby providing native promising sources for phytotherapy development.

Abbreviations

ABTS: 2,2ʹ-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid); AcOH: ethyl acetate; ANOVA: analysis of variance; SUS: Brazilian Unified Health System; DC-Mca: dichloromethane fraction from Mimosa caesalpiniifolia stem bark; DMSO: dimethylsulfoxide; DPPH: 1,1-diphenyl-2-picrylhydrazyl; EC₅₀: effective concentration 50%; EtOAc: ethyl acetate; FDA: Food and Drug Administration; GC-Qms: gas chromatograph quadrupole mass spectrometer; GI: genotoxic index; HCT-116: colon carcinoma line; HL-60: promyelocytic leukemia line; HPLC: high-performance liquid chromatography; HRAPCIMS: high resolution atmospheric pressure chemical ionization mass spectrum; IC₅₀: inhibitory concentration 50%; LC₅₀: lethal concentration 50%; MeOH = methyl alcohol; MI: mitotic index; MTT: 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide; MutI: mutagenic index; OVCAR-8 = ovarian carcinoma line; PBMC: peripheral blood mononuclear cells; RPMI-1640: Roswell Park Memorial Institute medium; SF-295: glioblastoma line; TEAC: trolox equivalent antioxidant capacity; TLC: thin-layer chromatography; Trolox: 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid

KEYWORDS:

• Oxidative stress
• antitumoral action
• genotoxicity
• cell cycle arrest
• environmental toxicology

Authorship contributions

JNS performed toxicity studies on Artemia salina, erythrocytes, peripheral blood mononuclear cells and Allium cepa. NNBM and AMGLC prepared samples from three plants and fractions from Mimosa caesalpiniifolia stem bark. RRSF, MHC, and MRSA prepared extracts from additional nine plants. DJBL and GCGM performed cytotoxic tests on human tumor lines. CP and RC managed funding supports. AL carried out antioxidant tests. ECCA isolated betulinic acid. PMPF planned the research, managed funding, and scientific supports, supervised all steps, analyzed the results, and wrote the article. All authors have read and agreed to the published version of the manuscript.

Acknowledgments

Dr Paulo Michel Pinheiro Ferreira (#303247/2019-3) and Dr Cláudia Pessoa (#303102/2013-6) are grateful to the “Conselho Nacional de Desenvolvimento Científico e Tecnológico” (CNPq) for their personal scholarships.

Disclosure statement

There are no conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome.

Ethics approval

All studies were executed in accordance with Brazilian guidelines (Law 466/2012, National Council of Health), the Declaration of Helsinki and with the Universal Declaration on Bioethics and Human Rights of UNESCO and were approved by the Human Research Ethical Committee of Federal University of Ceará (#0281/2019).

Submission declaration and verification

The work described has not been previously published or submitted for publication elsewhere. The publication is approved by all authors.

Supplementary material

Supplemental data for this article can be accessed on the publisher’s website.

Additional information

Funding

This investigation was partially supported by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior – Brasil (CAPES) - Finance Code 001.Dr Paulo Michel Pinheiro Ferreira (#303247/2019-3) and Dr Cláudia Pessoa (#303102/2013-6) are grateful to the Conselho Nacional de Desenvolvimento Científico e Tecnológico” (CNPq) for their personal scholarships.