A comparative chemoreactome analysis of choline alfoscerate and ethylmethylhydroxypyridine succinate molecules

   The combined use of neuroprotective agents and nootropic drugs with different mechanisms of action represents a promising avenue in the pharmacotherapy of impaired attention and memory, chronic cerebral ischemia, ischemic stroke, senile dementia and other conditions. A comparative chemoreactome study of choline alfoscerate (CA) and ethylmethylhydroxypyridine succinate (EMHPS) was conducted to identify the molecular mechanisms underlying the synergistic effects of these molecules at the level of the human proteome and reactome. The evaluation was carried out by analysing the chemical structures of CA and EMHPS using modern methods of complex data analysis (theories of labelled graph analysis, metric data analysis, combinatorial solvability theory, and topological theory of ill-formalized problem analysis), developed within the framework of an algebraic approach to recognition. Estimates have been obtained of the overall effects of CA and EMHPS on human reactome cascades, as well as of their effects on specific receptors in the human proteome, which underlie the molecules' general reactome effects. To establish the overall profiles of the effects of CA and EMHPS on the human reactome, a study was conducted on the effects of each of these molecules on 255 components of the reactome, including various signaling and metabolic cascades. The degree of effect on the human reactome was more pronounced for CA (0.62 ± 0.17 u.e.) than for EMHPS (0.54 ± 0.17 u.e.). A chemoreactome analysis of the studied molecules with specific receptor proteins of the human proteome included 1,052 target proteins (receptors for various ligands: neurotransmitters, hormones, signaling metabolites, etc.). The analysis showed that significant values for activation (EC50) and inhibition (IC50) constants were found for 67 receptor proteins, of which 20 receptors were activated and 47 receptors were inhibited. Receptors activated to a comparable degree by CA and EMHPS included cannabinoid, opioid, farnezoid and other receptors, which help reduce inflammation and pain, improve insulin secretion and counteract insulin resistance. Receptors activated pre-dominantly by EMHPS exert vasoregulatory, antidepressant, anxiolytic, antidiabetic and antihypoxic effects. Inhibition of proteome receptors by CA and EMHPS molecules (n = 47) corresponds to the anti-inflammatory, neuroprotective, analgesic, insulin-regulating, vasodynamic, antithrombotic and antitumour effects of the 'CA + EMHPS' combination. The identified mechanisms of the pharmacological and proteomic actions of CA and EMHPS indicate that the 'CA + EMHPS' combination exhibits synergistic neuroprotective and cardioprotective effects. The results obtained may be applied to any preparations whose active ingredients are CA and EMHPS, provided that the composition of active and excipient substances is identical.

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