Hesperidin, a flavonoid glycoside with sedative effect, decreases brain pERK1/2 levels in mice.

C. MARTINEZ; S. P. FERNANDEZ; L. M. LOSCALZO; C. WASOWSKI; A. C. PALADINI; M. MARDER; J. H MEDINA; H. VIOLA

PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR

Elsevier

Año: 2009 vol. 92 p. 291 - 296

0091-3057

The aim of this work was to evaluate if the intraperitoneal administration of the natural compound hesperidin, in a sedative dose, and neo-hesperidin, a hesperidin structural analog that exerts minor sedative effect, were able to induce changes in intracellular signaling cascades in different areas of the brain. The systemic administration of hesperidin produced a marked reduction in the phosphorylation state of extracellular signal-regulated kinases 1/2 (ERK 1/2), but not of Ca+2/calmodulin-dependent protein kinase II +2/calmodulin-dependent protein kinase II alfa subunit (alfaCaMKII), in the cerebral cortex, cerebellum and hippocampus. In contrast, neo-hesperidin did not markedly affect the activity of ERK 1/2 in both the cortex and the cerebellum. Taken together, these results demonstrated that intracellular signalling involving a selective decrease in ERK1/2 activation accompanied the depressant action of hesperidin. Even more, the low sedative action of neo-hesperidin correlates with a negligible decrease in phosphorylation state of ERK 1/2 (pERK 1/2), suggesting that low levels of pERK 1/2 in CNS could be a marker of sedative efficacy of flavonoids not markedly affect the activity of ERK 1/2 in both the cortex and the cerebellum.+2/calmodulin-dependent protein kinase II alfa subunit (alfaCaMKII), in the cerebral cortex, cerebellum and hippocampus. In contrast, neo-hesperidin did not markedly affect the activity of ERK 1/2 in both the cortex and the cerebellum. Taken together, these results demonstrated that intracellular signalling involving a selective decrease in ERK1/2 activation accompanied the depressant action of hesperidin. Even more, the low sedative action of neo-hesperidin correlates with a negligible decrease in phosphorylation state of ERK 1/2 (pERK 1/2), suggesting that low levels of pERK 1/2 in CNS could be a marker of sedative efficacy of flavonoids not markedly affect the activity of ERK 1/2 in both the cortex and the cerebellum.