title: Assessment of luteolin (3',4',5,7-tetrahydroxyflavone) neuropharmacological activity.
abstract: Since the discovery that certain flavonoids (namely flavones) specifically recognise the central BDZ receptors, several efforts have been made to identify naturally occurring GABA(A) receptor benzodiazepine binding site ligands. Flavonoid derivatives with a flavone-like structure such as apigenin, chrysin and wogonin have been reported for their anxiolytic-like activity in different animal models of anxiety. Luteolin (3',4',5,7-tetrahydroxyflavone) is a widespread flavonoid aglycon that was reported as devoid of specific affinity for benzodiazepine receptor (BDZ-R) binding site, but its psychopharmacological activity is presently unknown. Considering (1) the close structural similarity with other active flavones, (2) the activity of some of its glycosilated derivatives and (3) the complexity of flavonoid effects in the central nervous system, luteolin was submitted to a battery of tests designed to evaluate its possible activity upon the CNS and its ability to interact with the BDZ-receptor binding sites was also analysed. Luteolin apparently has CNS activity with anxiolytic-like effects despite the low affinity for the BDZ-R shown in vitro. Our findings suggest a possible interaction with other neurotransmitter systems but we cannot rule out the possibility that luteolin's metabolites might show a higher affinity for the BDZ-R in vivo, thus eliciting the evident anxiolytic-like effects through a GABAergic mechanism.
authors.affiliation: Laboratory of Pharmacognosy, Center for Pharmaceutical Studies, University of Coimbra, 3000 Coimbra, Portugal. mcoleta71@gmail.com
authors.forename: Miguel
authors.initials: M
authors.lastname: Coleta
authors.forename: Maria Graça
authors.initials: MG
authors.lastname: Campos
authors.forename: Maria Dulce
authors.initials: MD
authors.lastname: Cotrim
authors.forename: Thereza Christina M de
authors.initials: TC
authors.lastname: Lima
authors.forename: António Proença da
authors.initials: AP
authors.lastname: Cunha
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D001007:Anxiety / Q000517:prevention & control*; D001921:Brain / Q000187:drug effects*; D003975:Diazepam / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004353:Drug Evaluation, Preclinical; D005106:Exploratory Behavior / Q000187:drug effects*; D005419:Flavonoids / Q000494:pharmacology; D046352:Freezing Reaction, Cataleptic / Q000187:drug effects; D006993:Hypnotics and Sedatives / Q000494:pharmacology; D047311:Luteolin / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D011954:Receptors, Dopamine / Q000187:drug effects; D011963:Receptors, GABA-A / Q000187:drug effects*; D012018:Reflex / Q000187:drug effects
chemical_list: D000927:Anticonvulsants; D005419:Flavonoids; D006993:Hypnotics and Sedatives; D011954:Receptors, Dopamine; D011963:Receptors, GABA-A; D047311:Luteolin; D003975:Diazepam