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  • Maintenance of genomic integrity is complex due

    2020-07-31

    Maintenance of genomic integrity is complex due to the great diversity of damage that can occur in DNA. Deleterious consequences of damage accumulation may be avoided by a variety of DNA repair pathways, each recognizing and repairing specific types of DNA damage. Base excision repair (BER), nucleotide excision repair (NER), mismatch repair (MMR), homologous recombination (HR), non-homologous end-joining repair (NHEJ), single strand breaks repair (SSBR) and direct damage reversal repair are some of the most important pathways involved in the repair of oxidative and alkylating DNA damage (Kondo et al., 2010). The genus Hypericum contains a large number of sps that are widespread throughout Europe, West Asia, North Africa and North America. Hypericum sps. are widely used in traditional medicine due to their beneficial properties in the digestive and neurologic systems. Several biological activities, namely, antioxidant, antiproliferative, proapoptotic, anti-inflamatory, hepatoprotective and antidepressant activities have been attributed to some species of genus Hypericum (Savikin et al., 2007, Valentao et al., 2002, Xavier et al., 2012). Recently, Rainha and collaborators (Rainha et al., 2012) reported the phenolic composition of the aqueous extracts of some Hypericum species. The main constituents of H. perforatum (HP) are rutin (R), hyperoside, isoquercitrin, chlorogenic Fmoc-Arg(Pbf)-OH (Ch) and quercetin (Q). In H. androsaemum (HA), the main phenolic compound is Ch, followed by 3-caffeoylquinic acid, hyperoside, quercetin 3-sulfate, kaempferol, isoquercitrin, caffeoylquinic acid, R and Q that are less abundant. The major phenolic compounds present in the aqueous extract of H. undulatum (HU) are hyperoside, isoquercitrin, 3-caffeoylquinic acid, Ch and Q. Regarding their reported beneficial properties on the digestive tract, the aim of this study was to evaluate the effect of water extracts of three Hypericum sps., HP, HA, HU and some of the main phenolic compounds (Ch, R and Q) on DNA protection against oxidative and alkylating DNA damage induced by hydrogen peroxide (H2O2) and MMS, respectively in colon cells (HT29 cells). Effects on base excision repair and nucleotide excision repair pathways were also assessed in HT29 cells by in vitro repair assay using comet assay. This repair assay measures the excision repair activity of an extract prepared from HT29 cells pretreated with HP, HA, HU, Ch, R or Q by providing the cell extract with a DNA substrate from HeLa cells (agarose-embedded nucleoids) containing specific damage in this case induced by MMS. Increases in DNA damage prevention and/or repair activity by Hypericum extracts will indicate an anticarcinogenic potential of these plants.
    Materials and methods
    Results
    Discussion In this study, we demonstrated that Hypericum water extracts and some of the main constituents have antigenotoxic effects, protecting colon cells from oxidative and alkylating DNA damage and also inducing BER repair activity.