Potential role of opioid receptors on the effects of hesperidin and its aglycone hesperetin

LEONARDO M. LOSCALZO; CRISTINA WASOWSKI; MARIEL MARDER

Rosario, Argentina

Congreso; XLI Reunion Anual de la Sociedad Argentina de Farmacología Experimental; 2009

Hesperidin (HN, hesperetin-7-rhamnoglucoside) is a glycosilated flavanone present in Valeriana waliichi, V. officinalis, and Citrus species. Previous reports from our laboratory described the sedative and antinociceptive effects of HN in mice and the possible participation of the opioid system in these activities. In the present work we examined the involvement of 5-HT2A/C, á1 and á2-adrenergic and opioid receptors on the effect of HN in the hole board, locomotor activity and writhing tests. In order to advance in the study of the mechanism of action of HN, the capacity of this flavonoid, hesperetin (HN aglycone) and a set of natural and synthetic related compounds to bind to the ì opioid receptor was investigated. Additionally, the effect of HN and hesperetin on ì opioid receptor and GIRK1/2 channels co-expressed in Xenopus laevis oocytes was evaluated in electrophysiological experiments. The results indicated that HN is not a ligand for the ì opioid receptor but its in vivo effects are blocked by naltrexone (an opioid receptor antagonist). Hesperetin and other related flavonoids bind to the ì opioid receptor with Ki values between 1 to 120 ìM. These findings suggest an interaction between flavonoids and opioid receptors.