title: Chemical and biological characterisation of Machaerium hirtum (Vell.) Stellfeld: absence of cytotoxicity and mutagenicity and possible chemopreventive potential.
abstract: Machaerium hirtum (Vell.) Stellfeld (M.hirtum) is a plant known as 'jacarandá-bico-de-pato' whose bark is commonly used against diarrhea, cough and cancer. The aim of this study was to phytochemically characterise the hydroethanolic extract of this plant, investigate its antimutagenic activities using the Ames test and evaluate its effects on cell viability, genomic instability, gene expression and cell protection in human hepatocellular carcinoma cells (HepG2). Antimutagenic activity was assessed by simultaneous pre- and post-treatment with direct and indirect mutagens, such as 4-nitro-o-phenylenediamine (NPD), mitomycin C (MMC), benzo[a]pyrene (B[a]P) and aflatoxin B1 (AFB1), using the Ames test, cytokinesis blocking micronucleus and apoptosis assays. Only 3 of the 10 concentrations evaluated in the MTT assay were cytotoxic in HepG2 cells. Micronucleated or apoptotic cells were not observed with any of the tested concentrations, and there were no mutagenic effects in the bacterial system. However, the Nuclear Division Index and flow cytometry data showed a decrease in cell proliferation. The extract showed an inhibitory effect against direct (NPD) and indirect mutagens (B[a]P and AFB1). Furthermore, pre- and post-treated cells showed significant reduction in the number of apoptotic and micronucleated cells. This effect is not likely to be associated with the modulation of antioxidant genes, as shown by the RT-qPCR results. Six known flavonoids were identified in the hydroethanolic extract of Machaerium hirtum leaves, and their structures were elucidated by spectroscopic and spectrophotometric methods. The presence of the antioxidants apigenin and luteolin may explain these protective effects, because these components can inhibit the formation of reactive species and prevent apoptosis and DNA damage. In conclusion, the M.hirtum extract showed chemopreventive potential and was not hazardous at the tested concentrations in the experiments presented here. Moreover, this extract should be investigated further as a chemopreventive agent.
authors: Department of General Biology, Center of Biologic Sciences, State University of Londrina - UEL, Londrina, PR, Brazil.
authors: Diego Luis
authors: DL
authors: Ribeiro
authors: Department of General Biology, Center of Biologic Sciences, State University of Londrina - UEL, Londrina, PR, Brazil.
authors: Heloísa Lizotti
authors: HL
authors: Cilião
authors: Department of General Biology, Center of Biologic Sciences, State University of Londrina - UEL, Londrina, PR, Brazil.
authors: Ana Flávia Leal
authors: AF
authors: Specian
authors: Department of General Biology, Center of Biologic Sciences, State University of Londrina - UEL, Londrina, PR, Brazil, Department of Biological Sciences, Faculty of Pharmaceutical Sciences of Araraquara, São Paulo State University - UNESP, Araraquara, SP, Brazil.
authors: Juliana Mara
authors: JM
authors: Serpeloni
authors: Department of General Biology, Center of Biologic Sciences, State University of Londrina - UEL, Londrina, PR, Brazil.
authors: Marilesia Ferreira
authors: MF
authors: de Souza
authors: Coastal Campus, São Paulo State University - UNESP, São Vicente, SP, Brazil.
authors: Marcelo Marucci Pereira
authors: MM
authors: Tangerina
authors: Coastal Campus, São Paulo State University - UNESP, São Vicente, SP, Brazil.
authors: Wagner
authors: W
authors: Vilegas
authors: Department of Biological Sciences, Faculty of Pharmaceutical Sciences of Araraquara, São Paulo State University - UNESP, Araraquara, SP, Brazil.
authors: Paula Karina
authors: PK
authors: Boldrin
authors: Department of Biological Sciences, Faculty of Pharmaceutical Sciences of Araraquara, São Paulo State University - UNESP, Araraquara, SP, Brazil.
authors: Flávia Aparecida
authors: FA
authors: Resende
authors: Department of Biological Sciences, Faculty of Pharmaceutical Sciences of Araraquara, São Paulo State University - UNESP, Araraquara, SP, Brazil.
authors: Eliana Aparecida
authors: EA
authors: Varanda
authors: Institute of Biological Research Clemente Estable, Montevideo, Uruguay and.
authors: Wilner
authors: W
authors: Martínez-López
authors: School of Arts, Science and Humanities, São Paulo University-USP, São Paulo, SP, Brazil.
authors: Miriam
authors: M
authors: Sannomiya
authors: Department of General Biology, Center of Biologic Sciences, State University of Londrina - UEL, Londrina, PR, Brazil, ilcecolus@gmail.com.
authors: Ilce Mara Syllos
authors: IM
authors: Cólus
mesh_terms: D016587:Antimutagenic Agents / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D004249:DNA Damage / Q000187:drug effects; D007887:Fabaceae / Q000737:chemistry*; D005419:Flavonoids / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity; D005434:Flow Cytometry; D015870:Gene Expression; D006801:Humans; D048629:Micronuclei, Chromosome-Defective; D015162:Micronucleus Tests; D009152:Mutagenicity Tests; D009154:Mutation / Q000187:drug effects; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D012486:Salmonella typhimurium / Q000187:drug effects / Q000235:genetics
chemical_list: D016587:Antimutagenic Agents; D005419:Flavonoids; D010936:Plant Extracts