Abstract

BackgroundAn extract from Spatholobus suberectus (S. suberectus) Dunn has been reported to show potent antimutagenic effects against N-alkyl-N-nitrosoureas in umu screening. The aim of this study was to identify the antimutagenic components from extracts of S. suberectus against N-methyl-N-nitrosourea (MNU) in the Ames assay with Salmonella typhimurium strain TA1535 and to elucidate the antimutagenic mechanism of the flavonoids.ResultsFrom the ethyl acetate fraction obtained from fractionation of the methanol extract of S. suberectus Dunn, medicarpin, formononetin and isoliquiritigenin were successfully isolated through a combination of normal- and reversed-phase chromatography. Genistein and naringenin, which were already reported to be contained in S. suberectus Dunn, were also tested for their antimutagenicity towards MNU, along with formononetin, isoliquiritigenin and medicarpin. Our results demonstrated that genistein, isoliquiritigenin, medicarpin and naringenin were antimutagenic against MNU without showing cytotoxicity. MNU is reported to cause not only DNA alkylation but also induce reactive oxygen species. The hydroxyl radical scavenging capacity of the flavonoids was correlated with the antimutagenic capacity, indicating that the hydroxyl radical scavenging activity was involved in their antimutagenicity towards MNU.ConclusionsIt is important to prevent DNA damage by N-nitrosamines for cancer chemoprevention. Genistein, isoliquiritigenin, medicarpin and naringenin were demonstrated to possess an antigenotoxic effects against carcinogenic MNU due to their radical scavenging activity.

Highlights

  • N-Nitroso compounds, are implicated as carcinogens in the human environment such as food, tobacco smoke, air, water and cosmetics [1,2,3,4,5,6]

  • MNU is formed by the nitrosation of methylurea with nitrite in guinea-pig stomachs, and MNU is absorbed from the stomach into the blood [9]

  • Four components with antimutagenic activity against MNU from S. suberectus Dunn were identified as genistein, isoliquiritigenin, medicarpin, and naringenin

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Summary

Introduction

N-Nitroso compounds, are implicated as carcinogens in the human environment such as food, tobacco smoke, air, water and cosmetics [1,2,3,4,5,6]. N-nitroso compounds have been reported to be formed endogenously, mainly in the stomach and bowel, or in an infection site [2]. For chemoprevention, it is important to discover naturally occurring or synthetic compounds that. N-Methyl-N-nitrosourea (MNU) is a direct-acting mutagen that forms the corresponding methyldiazohydroxides and methylates DNA to form DNA adducts that miscode during DNA replication, causing mutations that lead to tumour formation. MNU can be detected by the nitrosation of creatinine or fermented foods at gastric pH [10,11,12]. For cancer chemoprevention, it is important to find some compounds that can inhibit the mutagenicity induced by MNU. An extract from Spatholobus suberectus (S. suberectus) Dunn has been reported to show potent antimutagenic effects against N-alkyl-N-nitrosoureas in umu screening. The aim of this study was to identify the antimutagenic components from extracts of S. suberectus against N-methyl-N-nitrosourea (MNU) in the Ames assay with Salmonella typhimurium strain TA1535 and to elucidate the antimutagenic mechanism of the flavonoids

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