HIPPOCAMPAL CHANGES IN ERK1/2 AFTER ADMIKNISTRATION OF HESPERIDIN, A BIOFLAVONOID WITH SEDATIVE-HYPNOTIC ACTIONS.

MARTINEZ MC; FERNANDEZ SP; WASOWSKI C; PALADINI AC; MEDINA JH; MARDER M; VIOLA H

Pinamar, Argentina.

Congreso; Congreso de la Sociedad Argentina de Neuroquímica; 2005

Inhibitory actions of flavonoids on kinase protein activity have been demonstrated. Hesperidin (HN), a flavanone glycoside isolated by us from Valeriana wallichii extracts, has sedative-hypnotic effects not related to the BDZ binding site in the GABAA-R. The aim of our work was to compare the sedative-hypnotic activity of HN in relation with its mechanism of action, in particular, its effects on intracellular protein kinases activity. Neo-HN, a structural analogue of HN, with less biological efficacy, was used as a control. After drug administrations and testing of their behavioural activity, mice were sacrificed and their hippocampi were dissected out and homogenized. Thereafter, 10% SDS-PAGE gels of protein extracts were performed and analyzed by western blot with pTyr, pERK1/2, ERK1/2 and pa-CamKII antibodies. There was a significative reduction in phosporylation levels of ERK1/2 in subjects treated with HN and, to a lesser extent, in the group treated with neo-HN. No changes were detected regarding phosphorylation of a-CaMKII. In conclusion, the sedative-hypnotic action of HN was associated with a decrease in ERK1/2 activity but not with a-CaMKII activity. A less effective analogue of HN induced lower changes in phosporylation levels. These results suggest that intracellular signalling involving ERK1/2 could be responsible of the depressant action of HN.