Genotoxicity-suppressing Effect of Aqueous Extract of Connarus ruber Cortex

Abstract

The anti-genotoxicity eSect of aqueous extracts of Connarus ruber cortex was studied in cultured human cells and mice. Connarus extract decreased bi-nuclei cells with micronuclei (MNBNC) signiˆcantly in NER-proˆcient WTK1 cells that were exposed to MNU, MMC, or UVC and in NER-deˆcient XPL3KA cells (that is, in XP-C) that were exposed to MNU or MMC, but not UVC. The genotoxicitysuppressing eSect was further studied by the comet assay. Connarus extract decreased DNA migration signiˆcantly in WTK1 cells that were exposed to MNU or UVC and in XPL3KA cells that were exposed to MNU but not UVC. In WTK1 cells, in contrast, DNA migration increased with the extract in the presence of DNA repair inhibitors (araC and HU), suggesting that the anti-genotoxic potential is due to an enhanced incision step of global genome repair (GGR) subpathways in NER. Chemical analysis revealed that the extract contains epicatechine, one of the anti-mutagenic components contained in green tea. Connarus extract fractions that decreased UVC-induced DNA migration were those not to contain epicatechine and they were diSerent from those that decreased MNU-induced DNA migration, suggesting that some anti-mutagenic components other than epicatechine might be contained in Connarus extract and that a number of anti-genotoxic components with diSerent modes of anti-genotoxicity are contained in Connarus extract. The anti-clastogenic eSect of Connarus extracts was examined in mice using a micronucleus assay. When mice received ≦2000 mg/kg Connarus extract by oral gavage at the same time as intraperitoneal injection of MMC, a decrease in the frequency of micronucleated reticulocytes was observed. This decrease was not due to a delay in the maturation of micronucleated reticulocytes.