Pigment and route of administration
Indicaxanthin belongs to the betalains, pigments present in Opuntia ficus-indica fruit. Allegra and colleagues isolated it from the pulp of a yellow-fruited variety and purified it chromatographically. In the pharmacokinetic part of the study, adult male Wistar rats received a single dose of 2 µmol of the compound per kilogram of body mass. The pigment was then measured in brain homogenates using HPLC. Before tissue collection, saline perfusion was performed to reduce the contribution of substance remaining in the blood. [Allegra et al. 2015]
The pigment was detected after one hour, reached its highest level after 2,5 hours, and was no longer detectable after 4 hours in the system used. These measurements document the compound's presence in tissue after oral administration and define its time course in this animal model. The publication separately describes an electrophysiological experiment using a different route of administration. [Allegra et al. 2015]
The response of an individual neuron
Hippocampal neuronal activity was recorded extracellularly in anaesthetised rats. A multichannel microelectrode also allowed indicaxanthin to be delivered near the recorded cell by microiontophoresis. 10 neurons were analysed for each of three amounts of the compound. The authors assessed firing rate, response onset latency and response duration. A vehicle control allowed the effect of the administration procedure itself to be assessed. [Allegra et al. 2015]
As the amount of the compound administered locally increased, inhibition of spontaneous firing increased in cells responding to treatment. At the highest amount tested, 0,34 ng per neuron, a significant fall in firing rate was found in 7 of 10 cells. Activity had to return to baseline for a recording to be included in the analysis. The result concerns acute, local exposure of neurons. [Allegra et al. 2015]
Glutamate and the receptor hypothesis
In the next stage, glutamate increased firing rate, while the simultaneous presence of indicaxanthin reduced this response. The authors combined the physiological observation with computer modelling of the pigment's interaction with the NMDA receptor. Docking identified possible binding sites and binding energetics. It provided a molecular hypothesis for further receptor experiments. [Allegra et al. 2015]
Detection of the compound in the brain after oral administration, inhibition of firing after microiontophoresis and the docking result describe three separate elements of the study. Together, they justify further investigation of the mechanism. Assessing the effects of fruit in the human diet would require direct studies of that exposure and appropriate endpoints. The publication discussed remains a preclinical study. [Allegra et al. 2015]
Based on scientific publications. The scope of the experiments is stated alongside the results.
Indicaxanthin from Opuntia ficus-indica Crosses the Blood–Brain Barrier and Modulates Neuronal Bioelectric Activity in Rat Hippocampus at Dietary-Consistent Amounts
Allegra M., Carletti F., Gambino G., Tutone M., Attanzio A., Tesoriere L., Ferraro G., Sardo P., Almerico A. M., Livrea M. A., Indicaxanthin from Opuntia ficus-indica Crosses the Blood–Brain Barrier and Modulates Neuronal Bioelectric Activity in Rat Hippocampus at Dietary-Consistent Amounts, Journal of Agricultural and Food Chemistry, 2015, 63(33):7353-7360, doi: 10.1021/acs.jafc.5b02612
A study of indicaxanthin in rats that includes measurement of the pigment in the brain after oral administration, recordings from hippocampal neurons during local microiontophoresis and modelling of interaction with the NMDA receptor. The results describe pharmacokinetics and the acute electrophysiological response in an animal model.