Meconic Acid Is a Possible Neuroprotector: Justification Based on in vitro Experiments and Its Physicochemical Properties

Meconic, comenic, chelidonic, and kojic acids are the main representatives of gamma-pyronic acids. It was found that comenic acid has a neuroprotective effect, and chelidonic acid has a pronounced anti-inflammatory effect. The neuroprotective effect of meconic acid has not been explored. The aim of this study was to investigate the neuroprotective potential of meconic acid on an in vitro ischemic stroke model, as well as on the basis of its physicochemical properties. A primary neuro-glial culture was obtained from the cerebellum of 7- to 8-day-old Wistar rats by mechanical dissociation. The protective effect of meconic acid on the culture of cerebellar neurons was studied using a model of glutamate toxicity and oxygen–glucose deprivation. The antioxidant activity of meconic acid was studied by quantum mechanical calculations and experimentally in the citrate-phosphate-luminol model system by chemiluminescence analysis. The chelating properties of meconic acid with respect to Fe 3+ in solutions were studied by the Job’s method. Meconic acid has been found to have a protective effect on in vitro models of ischemia. It caused a decrease in the level of intracellular calcium and restoration of the membrane potential of mitochondria in the culture of cerebellar neurons under glutamate exposure and an increase in the percentage of living cells under oxygen–glucose deprivation. Meconic acid had a high calculated antioxidant potential, as was confirmed experimentally. With an increase in pH of the medium, a stepwise binding of meconic acid with Fe 3+ occurred with the formation of complexes of different ligand/metal ratios. At physiological pH, the resulting complex had a composition with the ratio 1 : 3. The revealed antioxidant, chelating, and cytoprotective effects of meconic acid provide a basis for further study of the possible neuroprotective properties of this compound in experiments in vivo; the data on its physicochemical properties can be useful for the synthesis and study of new coordination compounds based on this acid.