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Synergistic interaction between hesperidin, a natural flavonoid, and diazepam

2005; Elsevier BV; Volume: 512; Issue: 2-3 Linguagem: Inglês

10.1016/j.ejphar.2005.02.039

1879-0712

Sebastián P. Fernández, Cristina Wasowski, Alejandro C. Paladini, Mariel Marder,

Piperaceae Chemical and Biological Studies

It has been recently reported the presence in Valeriana of the flavone 6-methylapigenin and the flavanone glycoside hesperidin. The apigenin derivative is a ligand for the benzodiazepine binding site in the γ-aminobutyric acid receptor type A (GABAA) and has anxiolytic properties. Hesperidin has sedative and sleep-enhancing properties but is not a ligand for the benzodiazepine binding site. 6-Methylapigenin is able to potentiate the sleep-enhancing effect of hesperidin. In this work we demonstrate that this property is shared with various GABAA receptor ligands, among them the agonist diazepam, which was used to study the potentiation as measured in the hole board test. Isobolar analysis of the results showed the interaction being synergistic. We discarded pharmacokinetic effects or a direct action of hesperidin on the benzodiazepine binding site. A possible use of hesperidin properties to decrease the effective therapeutic doses of benzodiazepines is suggested.