Abstract
The central nervous system (CNS) is a mythical target for drug delivery. There is an ongoing debate over the brain accessibility of flavonoids, a group of plant-derived secondary metabolites widely known by their multifarious bioactivities achieved by distinct mechanisms. Recently, their applicability in the management of neurologic and psychiatric disorders, such as Alzheimer’s and Parkinson’s diseases, and major depression, has received particular attention. To reach their target, flavonoids must cross over the ultimate obstacle - the blood-brain barrier - at pharmacologically effective concentrations. This review addresses the low brain-bioavailability issue, based on in vitro and in vivo evidences. Besides the lipophilic character of the flavonoids, their permeability will depend upon the role of membrane transporters, especially those from the ABC superfamily. The enzymatic elements, namely β-glucuro-nidase, can induce a transient deconjugation process and affect permeability, as well. Novel drug delivery systems are successful strategies to overcome the low bioavailability issue, and redirect the native forms to CNS-targets. This work bridges a solid opinion over this hot topic of medicinal chemistry and natural products research.
Keywords: Flavonoids, brain-delivery, blood-brain-barrier, permeability, transporters, nano-carriers, neurodegeneration.
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