DNA-protective activities of hyperforin and aristoforin

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 topoi...

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Bibliographic Details
Published in:Toxicology in vitro Vol. 29; no. 3; pp. 631 - 637
Main Authors: Ševčovičová, A., Šemeláková, M., Plšíková, J., Loderer, D., Imreová, P., Gálová, E., Kožurková, M., Miadoková, E., Fedoročko, P.
Format: Journal Article
Language:English
Published: England Elsevier Ltd 01-04-2015
Subjects:
Antioxidants - pharmacology
Aristoforin
DNA - drug effects
DNA Breaks - drug effects
DNA unwinding assay
DNA-topology assay
DPPH[rad]/[rad]OH scavenging activity
Free Radical Scavengers - pharmacology
Hyperforin
Hypericum - chemistry
Hypericum perforatum
Iron - toxicity
Iron Chelating Agents - pharmacology
Phloroglucinol - analogs & derivatives
Phloroglucinol - pharmacology
Reducing power assay
Terpenes - pharmacology
Topoisomerase I Inhibitors - pharmacology
Reducing power assay
Hyperforin
Aristoforin
DNA unwinding assay
DNA-topology assay
DPPH/OH scavenging activity
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Summary:•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 0.2×108M−1. We suggest that a mechanism of hyperforin/aristoforin DNA-protective abilities is based on free radicals (mainly OH) scavenging activity.
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ISSN:0887-2333
1879-3177
DOI:10.1016/j.tiv.2015.01.016