DNA-protective activities of hyperforin and aristoforin

• Mechanisms of hyperforin and aristoforin DNA-protective activities were studied in vitro.
• Both chemicals protect DNA against Fe2+-induced DNA breaks.
• Mechanism of DNA protection is based on their activity to scavenge free radicals, mainly OH.
• Hyperforin and aristoforin are not able to inhibit topoisomerase I.
• Hyperforin and aristoforin could not intercalate into DNA.

The aim of this study was to explain the molecular mechanisms of action of hyperforin, a phluoroglucinol derivative found in Hypericum perforatum L. and its more stable derivative aristoforin. DNA-topology assay revealed partial DNA-protective activities of hyperforin and aristoforin against Fe2+-induced DNA breaks. In order to assess molecular mechanisms underlying DNA-protective activity, the potential antioxidant activity of hyperforin and aristoforin was investigated using DPPH and OH scavenging assays, reducing power assay and Fe2+-chelating assay. We also studied interaction of hyperforin and aristoforin with DNA using established protocols for fluorescence titration. The ability of the studied compounds to relax topoisomerase I with electrophoretic techniques was investigated. The reduction in the fluorescence of hyperforin indicated an interaction between hyperforin and DNA with a binding constant of 0.2 × 108 M−1. We suggest that a mechanism of hyperforin/aristoforin DNA-protective abilities is based on free radicals (mainly OH) scavenging activity.