Effects of Hesperidin and Nepitrin (Salvia rosmarinus) on the Response of GABAA Receptors Expressed in Xenopus Oocytes and their Neuropharmacological Activities

Salvia rosmarinus, previously known as Rosmarinus officinalis, has intense pleasant smell reminiscent of pine wood. S. rosmarinus has been widely used in traditional medicines and has long been known as the herb of remembrance. However, few studies have investigated the effects of non-volatile components of rosemary on central nervous system function. In this study, Bio-assay guided fractionation of the butanolic extract of S. rosmarinus led to the isolation of two compounds hesperidin and nepitrin. Hesperidin and nepitrin were evaluated on recombinant α1β2γ2L GABAA receptors expressed in Xenopus laevis oocytes. Hesperidin and nepitrin were found to be flumazenil insensitive negative allosteric modulators of high concentrations of GABA at a1b2g2L GABAA receptors. Hesperidin and nepitrin allosterically inhibit the response of GABA at a1b2g2L GABA receptors via a site other than the high-affinity benzodiazepine biding site.