In vitro DNA protective properties of silybin and analogues against X-ray radiation induced damage

Abstract

Natural flavonoids such as silybin (SLB), hesperetin (HESP), naringenin (NAN) and naringin( NAR) are believed to be active constituents of plants accounting for the reported chemoprevention of certain cancers. However, the molecular mechanisms by which the low concentrations of silybin and analogues in human can reduce the incidence are not clear. Using an in vitro plasmid DNA system and radiolytically generating reactive oxygen species (ROS) under constant scavenging conditions, we have shown that the four flavonoids are able to ameliorate free radical damage sustained by DNA. The dose modifying factor for 0.1 mM SLB for 50 percent protection of the plasmid DNA was found to be 8.9. SLB was found to be the most active among the tested flavonoids, with effects seen at micromolar concentrations. Combined fast-reaction chemistry studies support a mechanism of electron transfer (or H-atom transfer) from silybin to ROS-induced radical sites on the DNA. These results support an antioxidant role for silybin and analogues in the direct interaction with DNA radicals.