title: Indicaxanthin from Opuntia ficus-indica Crosses the Blood-Brain Barrier and Modulates Neuronal Bioelectric Activity in Rat Hippocampus at Dietary-Consistent Amounts.
abstract: Indicaxanthin is a bioactive and bioavailable betalain pigment from the Opuntia ficus-indica fruits. In this in vivo study, kinetic measurements showed that indicaxanthin is revealed in the rat brain within 1 h from oral administration of 2 μmol/kg, an amount compatible with a dietary consumption of cactus pear fruits in humans. A peak (20 ± 2.4 ng of indicaxanthin per whole brain) was measured after 2.5 h; thereafter the molecule disappeared with first order kinetics within 4 h. The potential of indicaxanthin to affect neural activities was in vivo investigated by a microiontophoretic approach. Indicaxanthin, administered in a range between 0.085 ng and 0.34 ng per neuron, dose-dependently modulated the rate of discharge of spontaneously active neurons of the hippocampus, with reduction of the discharge and related changes of latency and duration of the effect. Indicaxanthin (0.34 ng/neuron) showed inhibitory effects on glutamate-induced excitation, indicating activity at the level of glutamatergic synapses. A molecular target of indicaxanthin is suggested by in silico molecular modeling of indicaxanthin with N-methyl-D-aspartate receptor (NMDAR), the most represented of the glutamate receptor family in hippocampus. Therefore, at nutritionally compatible amounts indicaxanthin (i) crosses the rat BBB and accumulates in brain; (ii) can affect the bioelectric activity of hippocampal neurons locally treated with amounts comparable with those measured in the brain; and (iii) modulates glutamate-induced neuronal excitation. The potential of dietary indicaxanthin as a natural neuromodulatory agent deserves further mechanistic and neurophysiologic investigation.
authors.affiliation: Dipartimento di Scienze e Tecnologie Biologiche, Chimiche e Farmaceutiche, University of Palermo , Via M. Cipolla 74, 90121 Palermo, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Allegra
authors.affiliation: Dipartimento di Biomedicina Sperimentale e Neuroscienze Cliniche, Sezione di Fisiologia Umana "G. Pagano", University of Palermo , Corso Tukory 129, 90134 Palermo, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Carletti
authors.affiliation: Dipartimento di Biomedicina Sperimentale e Neuroscienze Cliniche, Sezione di Fisiologia Umana "G. Pagano", University of Palermo , Corso Tukory 129, 90134 Palermo, Italy.
authors.forename: Giuditta
authors.initials: G
authors.lastname: Gambino
authors.affiliation: Dipartimento di Scienze e Tecnologie Biologiche, Chimiche e Farmaceutiche, University of Palermo , Via M. Cipolla 74, 90121 Palermo, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Tutone
authors.affiliation: Dipartimento di Scienze e Tecnologie Biologiche, Chimiche e Farmaceutiche, University of Palermo , Via M. Cipolla 74, 90121 Palermo, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Attanzio
authors.affiliation: Dipartimento di Scienze e Tecnologie Biologiche, Chimiche e Farmaceutiche, University of Palermo , Via M. Cipolla 74, 90121 Palermo, Italy.
authors.forename: Luisa
authors.initials: L
authors.lastname: Tesoriere
authors.affiliation: Dipartimento di Biomedicina Sperimentale e Neuroscienze Cliniche, Sezione di Fisiologia Umana "G. Pagano", University of Palermo , Corso Tukory 129, 90134 Palermo, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Ferraro
authors.affiliation: Dipartimento di Biomedicina Sperimentale e Neuroscienze Cliniche, Sezione di Fisiologia Umana "G. Pagano", University of Palermo , Corso Tukory 129, 90134 Palermo, Italy.
authors.forename: Pierangelo
authors.initials: P
authors.lastname: Sardo
authors.affiliation: Dipartimento di Scienze e Tecnologie Biologiche, Chimiche e Farmaceutiche, University of Palermo , Via M. Cipolla 74, 90121 Palermo, Italy.
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Almerico
authors.affiliation: Dipartimento di Scienze e Tecnologie Biologiche, Chimiche e Farmaceutiche, University of Palermo , Via M. Cipolla 74, 90121 Palermo, Italy.
authors.forename: Maria Antonia
authors.initials: MA
authors.lastname: Livrea
mesh_terms: D000818:Animals; D050860:Betaxanthins / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D001812:Blood-Brain Barrier / Q000187:drug effects*; D004594:Electrophysiology / Q000379:methods; D006624:Hippocampus / Q000187:drug effects* / Q000502:physiology*; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D029747:Opuntia / Q000737:chemistry*; D011725:Pyridines / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D017208:Rats, Wistar; D017470:Receptors, Glutamate / Q000378:metabolism
chemical_list: D050860:Betaxanthins; D011725:Pyridines; D017470:Receptors, Glutamate; C469628:indicaxanthin
keywords: BBB; electrophysiology; hippocampus; indicaxanthin; microiontophoresis; molecular modeling; phytochemicals