In vitro binding affinities of a series of flavonoids for μ-opioid receptors. Antinociceptive effect of the synthetic flavonoid 3,3-dibromoflavanone in mice.

The pharmacotherapy for the treatment of pain is an active area of investigation. There are effective drugs to treat this problem, but there is also a need to find alternative treatments free of undesirable side effects. In the present work the capacity of a series of flavonoids to bind to the μ opioid receptor was evaluated.

Chronic intraperitoneal and oral treatments with hesperidin induce central nervous system effects in mice.

Hesperidin (HN) is a flavanone glycoside abundantly found in citrus fruits. This flavonoid mediated central nervous system activity following intraperitoneal (i.p.

Hesperidin induces antinociceptive effect in mice and its aglycone, hesperetin, binds to μ-opioid receptor and inhibits GIRK1/2 currents.

This paper extended the evaluation of the depressant and antinociceptive activities of hesperidin in order to determine its effectiveness by the intraperitoneal and oral routes, its pharmacological interaction with diverse pathways of neurotransmission and the role of its aglycone, hesperetin. The capacity of hesperidin and hesperetin to bind to μ-opioid receptor and their actions on μ-opioid receptor co-expressed with GIRK1/GIRK2 channels (G protein-activated inwardly rectifying K+ channels) in Xenopus laevis oocytes were also determined. Hesperidin exhibited a depressant activity in the hole board and locomotor activity tests, antinociceptive activities in the abdominal writhing and hot plate tests and no motor incoordination in the inverted screen and rotarod assays, only by the intraperitoneal route.

Neuroactive flavonoid glycosides from Tilia petiolaris DC. extracts.

Pharmacological assay guided purification of an ethanol extract of Tilia petiolaris DC. inflorescences resulted in the isolation and identification of isoquercitrin (ISO), quercetin 3-O-glucoside-7-O-rhamnoside (QUE) and kaempferol 3-O-glucoside-7-O-rhamnoside (KAE). The behavioral actions of these glycosylated flavonoids were examined in the hole board, locomotor activity and thiopental-induced loss of righting reflex tests in mice.

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 (alphaCaMKII), 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.

Opioid receptors are involved in the sedative and antinociceptive effects of hesperidin as well as in its potentiation with benzodiazepines.

Previous reports from our laboratory described the sedative activity of hesperidin (hesperetin-7-rhamnoglucoside). This property is greatly increased when the glycoside is injected jointly with diazepam and this interaction has been shown to be synergistic. In the present work the generality of the synergistic phenomenon is proved, since potentiation also occurs with several other benzodiazepines, namely alprazolam, bromazepam, midazolam and flunitrazepam.

Central nervous system depressant action of flavonoid glycosides.

The pharmacological effects on the central nervous system (CNS) of a range of available flavonoid glycosides were explored and compared to those of the glycosides 2S-hesperidin and linarin, recently isolated from valeriana. The glycosides 2S-neohesperidin, 2S-naringin, diosmin, gossipyn and rutin exerted a depressant action on the CNS of mice following i.p.