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Open Access Research article

Mutagenicity and antimutagenicity of (−)-hinokinin a trypanosomicidal compound measured by Salmonella microsome and comet assays

Flávia Aparecida Resende1*, Lilian Cristina Barbosa2, Denise Crispim Tavares2, Mariana Santoro de Camargo1, Karen Cristina de Souza Rezende2, Márcio Luis de Andrade e Silva2 and Eliana Aparecida Varanda1

Author affiliations

1 Departamento de Ciências Biológicas, UNESP-Universidade Estadual Paulista Julio de Mesquita Filho- Faculdade de Ciências Farmacêuticas de Araraquara, Araraquara, São Paulo, 14801-902, Brazil

2 Universidade de Franca, Franca, São Paulo, 14404-600, Brazil

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Citation and License

BMC Complementary and Alternative Medicine 2012, 12:203  doi:10.1186/1472-6882-12-203

Published: 31 October 2012

Abstract

Background

The dibenzylbutyrolactone lignan (−)-hinokinin (HK) was derived by partial synthesis from (−)-cubebin, isolated from the dry seeds of the pepper, Piper cubeba. Considering the good trypanosomicidal activity of HK and recalling that natural products are promising starting points for the discovery of novel potentially therapeutic agents, the aim of the present study was to investigate the (anti) mutagenic∕ genotoxic activities of HK.

Methods

The mutagenic∕ genotoxic activities were evaluated by the Ames test on Salmonella typhimurium strains TA98, TA97a, TA100 and TA102, and the comet assay, so as to assess the safe use of HK in the treatment of Chagas’ disease. The antimutagenic ∕antigenotoxic potential of HK were also tested against the mutagenicity of a variety of direct and indirect acting mutagens, such as 4- nitro-o-phenylenediamine (NOPD), sodium azide (SA), mitomycin C (MMC), benzo[a]pyrene (B[a]P), aflatoxin B1 (AFB1), 2-aminoanthracene (2-AA) and 2-aminofluorene (2-AF), by the Ames test, and doxorubicin (DXR) by the comet assay.

Results

The mutagenicity∕genotoxicity tests showed that HK did not induce any increase in the number of revertants or extent of DNA damage, demonstrating the absence of mutagenic and genotoxic activities. On the other hand, the results on the antimutagenic potential of HK showed a strong inhibitory effect against some direct and indirect-acting mutagens.

Conclusions

Regarding the use of HK as an antichagasic drug, the absence of mutagenic effects in animal cell and bacterial systems is encouraging. In addition, HK may be a new potential antigenotoxic ∕ antimutagenic agent from natural sources. However, the protective activity of HK is not general and varies with the type of DNA damage-inducing agent used.

Keywords:
Hinokinin; Ames test; Comet assay; Mutagenicity; Antimutagenicity