Flavonoids and the central nervous system: from forgotten factors to potent anxiolytic compounds

The list of activities of plant flavonoids did not include effects on the c entral nervous system (CNS) up to 1990, when our laboratory described the e xistence of natural anxiolytic flavonoids. The first of these was chrysin ( 5,7-dihydroxyflavone), followed by apigenin (5,7,4'-trihydroxyflavone) and flavone itself. Semisynthetic derivatives of flavone obtained by introducin g halogens, nitro groups or both in its molecule, give rise to high affinit y ligands for the benzodiazepine receptor, active in-vivo; 6,3'-dinitroflav one, for example, is an anxiolytic drug 30 times more potent than diazepam. The data collected in this paper make clear that some natural flavonoids ar e CNS-active molecules and that the chemical modification of the flavone nu cleus dramatically increases their anxiolytic potency.