Assessment of DNA damage by extracts and fractions of Strychnos pseudoquina, a Brazilian medicinal plant with antiulcerogenic activity F.V. Santos a , I.M.S. Colus b , M.A. Silva c , W. Vilegas c , E.A. Varanda a, * a Department of Biological Sciences, Faculty of Pharmaceutical Sciences of Araraquara, Sa ˜o Paulo State University, UNESP, SP, Brazil b Department of General Biology, Biological Sciences Center, State University of Londrina, PR, Brazil c Chemical Institute of Araraquara, Sa ˜o Paulo State University, UNESP, SP, Brazil Received 11 January 2006; accepted 29 March 2006 Abstract Strychnos pseudoquina St. Hil. is a native plant of the Brazilian Savannah, used in popular medicine to treat a number of conditions. Since it contains large quantities of alkaloids with proven antiulcer activity, we tested the genotoxic potential of crude extracts and fractions containing alkaloids and flavonoids from the leaves of this plant, on Salmonella typhimurium and performed the micronucleus test on peripheral blood cells of mice treated in vivo. The results showed that the methanol extract of the leaves of S. pseudoquina is mutagenic to the TA98 (ÀS9) and TA100 (+S9, ÀS9) strains of Salmonella. The dichloromethane extract was not mutagenic to any of the tested strains. Fractions enriched with alkaloids or flavonoids were not mutagenic. In vivo tests were done on the crude methanol extract in albino Swiss mice, which were treated, by gavage, with three different doses of the extract. The highest dose tested (1800 mg/ kg b.w.) induced micronuclei after acute treatment, confirming the mutagenic potential of the methanol extract of the leaves of S. pseud- oquina. In high doses, constituents of S. pseudoquina compounds act on DNA, causing breaks and giving rise to micronuclei in the blood cells of treated animals. Ó 2006 Elsevier Ltd. All rights reserved. Keywords: Strychnos pseudoquina; Mutagenicity; Salmonella typhimurium; Micronucleus; Ames test 1. Introduction The Strychnos genus (Family Loganiaceae) includes about 200 plant species distributed in the tropical regions of the globe (Philippe et al., 2004; Thongphasuk et al., 2003). Many of these species are known for their medicinal potential and feature powerful poisons among their secondary metabolites. The most famous and powerful of these poisons is strychnine, one of many indole alkaloids produced by plants of this genus (Thongphasuk et al., 2003; Philippe et al., 2004). Strychnos pseudoquina St. Hil. is a native cinchona-like tree of the Brazilian Savannah (Cerrado), popularly used for the treatment of hepatic and stomach diseases (Correa, 1926), fevers and malaria (Andrade-Neto et al., 2003). Phy- tochemical studies on plants of this species have demon- strated the presence of alkaloids and flavonoids (Nicoletti et al., 1984; Silva et al., 2005). Many alkaloids are known to be genotoxic (Mori et al., 1985; Wang and Peng, 1996; Mei et al., 2004; Ansah et al., 2005). However, many of these alkaloids have also demon- strated an outstanding pharmacological potential, exhibit- ing antimicrobial, antiplasmodial and antitumoral activities (Frederich et al., 1999; Kingston et al., 1978). In the case of the flavonoids, despite many results indicating their pharmacological activity and potential benefit to 0278-6915/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved. doi:10.1016/j.fct.2006.03.012 * Corresponding author. Tel.: +55 16 3301 6951; fax: +55 16 3301 6940. E-mail address: varandae@fcfar.unesp.br (E.A. Varanda). www.elsevier.com/locate/foodchemtox Food and Chemical Toxicology 44 (2006) 1585–1589