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

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 alpha subunit (alpha CaMKII), 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. (C) 2008 Elsevier Inc. All rights reserved.