Abstract
Several studies have recently investigated the role of nutraceuticals in complex pathophysiological processes such as oxidative damages, inflammatory conditions and excitotoxicity. In this regard, the effects of nutraceuticals on basic functions of neuronal cells, such as excitability, are still poorly investigated. For this reason, the possible modulation of neuronal excitability by phytochemicals (PhC) could represent an interesting field of research given that excitotoxicity phenomena are involved in neurodegenerative alterations leading, for example, to Alzheimer’s disease. The present study was focused on indicaxanthin from Opuntia ficus indica, a bioactive betalain pigment, with a proven antioxidant and anti-inflammatory potential, previously found to cross blood-brain barrier (BBB) and to modulate the bioelectric activity of hippocampal neurons. On this basis, we aimed at detecting the specific brain areas where indicaxanthin localizes after oral administration at dietary-achievable amounts and highlighting eventual local effects on the excitability of single neuronal units. HPLC analysis of brain tissue 1 h after ingestion of 2 μmol/kg indicaxanthin indicated that the phytochemical accumulates in cortex, hippocampus, diencephalon, brainstem and cerebellum, but not in the striato-pallidal complex. Then, electrophysiological recordings, applying the microiontophoretic technique, were carried out with different amounts of indicaxanthin (0.34, 0.17, 0.085 ng/neuron) to assess whether indicaxanthin influenced the neuronal firing rate. The data showed that the bioelectric activity of neurons belonging to different brain areas was modulated after local injection of indicaxanthin, mainly with dose-related responses. A predominating inhibitory effect was observed, suggesting a possible novel beneficial effect of indicaxanthin in reducing cell excitability. These findings can constitute a new rationale for exploring biological mechanisms through which PhC could modulate neuronal function with a relapse on complex cognitive brain process and related neurodegenerative conditions.
Highlights
In the recent years a growing bulk of studies expanded knowledge about the positive impact of dietary phytochemicals (PhC), or nutraceuticals, on complex physiological processes and brain aging
We demonstrate for the first time that indicaxanthin, a betalain pigment able to cross the blood-brain barrier (BBB) (Allegra et al, 2015), when administered at nutritionally-relevant amounts accumulates within different brain areas and remains unmodified at levels comparable or even greater than those showed by other PhC (Vingtdeux et al, 2010; Vanmierlo et al, 2012)
While some PhC distribute within the brain homogeneously (Milbury and Kalt, 2010), we here show that indicaxanthin gains a specific access to selected brain areas
Summary
In the recent years a growing bulk of studies expanded knowledge about the positive impact of dietary phytochemicals (PhC), or nutraceuticals, on complex physiological processes and brain aging. More recently a multidisciplinary approach has demonstrated that indicaxanthin orally administered at dietaryrelevant doses is able to cross blood-brain barrier (BBB) and accumulate within the rat brain; beyond this, the intriguing ability of this phytochemical to modulate the bioelectric activity of hippocampal neurons for the first time has emerged (Allegra et al, 2015). In this light, the current research aimed to detect a brain distribution pattern of indicaxanthin, after oral administration of nutritionally-relevant amounts, by HPLC assay. Afterwards, microiontophoretic recordings were carried out to explore a possible influence of the indicaxanthin on the bioelectric activity of single neuronal units in specific brain areas
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