PMID- 26227670 OWN - NLM STAT- MEDLINE DCOM- 20160412 LR - 20220321 IS - 1520-5118 (Electronic) IS - 0021-8561 (Linking) VI - 63 IP - 33 DP - 2015 Aug 26 TI - Indicaxanthin from Opuntia ficus-indica Crosses the Blood-Brain Barrier and Modulates Neuronal Bioelectric Activity in Rat Hippocampus at Dietary-Consistent Amounts. PG - 7353-60 LID - 10.1021/acs.jafc.5b02612 [doi] AB - 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 mumol/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. FAU - Allegra, Mario AU - Allegra M AD - Dipartimento di Scienze e Tecnologie Biologiche, Chimiche e Farmaceutiche, University of Palermo , Via M. Cipolla 74, 90121 Palermo, Italy. FAU - Carletti, Fabio AU - Carletti F AD - Dipartimento di Biomedicina Sperimentale e Neuroscienze Cliniche, Sezione di Fisiologia Umana "G. Pagano", University of Palermo , Corso Tukory 129, 90134 Palermo, Italy. FAU - Gambino, Giuditta AU - Gambino G AD - Dipartimento di Biomedicina Sperimentale e Neuroscienze Cliniche, Sezione di Fisiologia Umana "G. Pagano", University of Palermo , Corso Tukory 129, 90134 Palermo, Italy. FAU - Tutone, Marco AU - Tutone M AD - Dipartimento di Scienze e Tecnologie Biologiche, Chimiche e Farmaceutiche, University of Palermo , Via M. Cipolla 74, 90121 Palermo, Italy. FAU - Attanzio, Alessandro AU - Attanzio A AD - Dipartimento di Scienze e Tecnologie Biologiche, Chimiche e Farmaceutiche, University of Palermo , Via M. Cipolla 74, 90121 Palermo, Italy. FAU - Tesoriere, Luisa AU - Tesoriere L AD - Dipartimento di Scienze e Tecnologie Biologiche, Chimiche e Farmaceutiche, University of Palermo , Via M. Cipolla 74, 90121 Palermo, Italy. FAU - Ferraro, Giuseppe AU - Ferraro G AD - Dipartimento di Biomedicina Sperimentale e Neuroscienze Cliniche, Sezione di Fisiologia Umana "G. Pagano", University of Palermo , Corso Tukory 129, 90134 Palermo, Italy. FAU - Sardo, Pierangelo AU - Sardo P AD - Dipartimento di Biomedicina Sperimentale e Neuroscienze Cliniche, Sezione di Fisiologia Umana "G. Pagano", University of Palermo , Corso Tukory 129, 90134 Palermo, Italy. FAU - Almerico, Anna Maria AU - Almerico AM AD - Dipartimento di Scienze e Tecnologie Biologiche, Chimiche e Farmaceutiche, University of Palermo , Via M. Cipolla 74, 90121 Palermo, Italy. FAU - Livrea, Maria Antonia AU - Livrea MA AD - Dipartimento di Scienze e Tecnologie Biologiche, Chimiche e Farmaceutiche, University of Palermo , Via M. Cipolla 74, 90121 Palermo, Italy. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150813 PL - United States TA - J Agric Food Chem JT - Journal of agricultural and food chemistry JID - 0374755 RN - 0 (Betaxanthins) RN - 0 (Pyridines) RN - 0 (Receptors, Glutamate) RN - 0 (indicaxanthin) SB - IM MH - Animals MH - Betaxanthins/administration & dosage/pharmacokinetics/*pharmacology MH - Blood-Brain Barrier/*drug effects MH - Electrophysiology/methods MH - Hippocampus/*drug effects/*physiology MH - Male MH - Neurons/drug effects/physiology MH - Opuntia/*chemistry MH - Pyridines/administration & dosage/pharmacokinetics/*pharmacology MH - Rats, Wistar MH - Receptors, Glutamate/metabolism OTO - NOTNLM OT - BBB OT - electrophysiology OT - hippocampus OT - indicaxanthin OT - microiontophoresis OT - molecular modeling OT - phytochemicals EDAT- 2015/08/01 06:00 MHDA- 2016/04/14 06:00 CRDT- 2015/08/01 06:00 PHST- 2015/08/01 06:00 [entrez] PHST- 2015/08/01 06:00 [pubmed] PHST- 2016/04/14 06:00 [medline] AID - 10.1021/acs.jafc.5b02612 [doi] PST - ppublish SO - J Agric Food Chem. 2015 Aug 26;63(33):7353-60. doi: 10.1021/acs.jafc.5b02612. Epub 2015 Aug 13.