Synergism of magnesium- and pyridoxine-dependent proteins in nervous system support: systems biological analysis

Background. For magnesium–pyridoxine therapy (original drug Magne B6®), the systems-level proteomic synergy of magnesium and pyridoxine-dependent proteins remains to be not sufficiently characterized in the nervous systems of pregnant women and diverse age groups.
Objective: To establish the mechanisms of action of magnesium-dependent proteins on human neurophysiology and to characterize the proteomic synergy of original product components (a fixed combination of magnesium lactate and pyridoxine).
Material and methods. In order to compile the most comprehensive list of magnesium- and pyridoxine-dependent proteins, the study applied algorithms for genome/proteome annotation and heterogeneous feature analysis, developed within the topological recognition theory. Subsequent analyses were conducted using data such as annotation keywords, protein tissue distribution, other protein cofactors, roles in the reactom, functional categories, protein interactions with various pharmaceuticals (including other micronutrients and nutraceuticals), and diseases associated with impaired magnesium-dependent protein activity.
Results. The study identified a comprehensive set of magnesium- (n=1020) and pyridoxine-dependent (n=99) proteins, with a specific focus on those involved in nervous system function. Among various tissues, the brain exhibits the greatest diversity of magnesiumdependent (n=244) proteins. The synergy between magnesium and pyridoxine is manifested across many levels: cofactor interactions, protein functional categories, interactions with various pharmaceuticals, and associations with diseases. Notably, many pyridoxinedependent proteins interact with the same cofactors as magnesium-dependent proteins. Pyridoxine-dependent proteins generally fall into the same most common functional categories as magnesium-dependent ones, indicating a clear synergism between magnesium and pyridoxine in supporting fundamental physiological processes. At least 172 magnesium-dependent proteins and 20 pyridoxinedependent proteins in the human proteome are involved in the neuroprotective, neurotrophic, and other neurotropic effects of magnesium. These proteins play an important role in maintaining neurotransmitter homeostasis, neuroplasticity, and neuronal survival. Furthermore, a total of 143 drugs (including a number of micronutrients and/or nutraceuticals) are associated with the function/activity of magnesium-dependent proteins; these encompass anesthetics, anxiolytics, hypnotics and sedatives, antidementia drugs, calcium channel blockers, cardiac glycosides, antiarrhythmic agents and other cardiac drugs, antidepressants, antipsychotics, antibiotics, etc. The interaction of magnesium-dependent proteins with these groups of drugs is multidirectional. Analysis of diseases associated with dysfunction of magnesium-dependent proteins in the human proteome revealed at least 80 different diseases associated with magnesium deficiency (seizures; impaired fetal neurological development; myelination of nerves; impaired vision, hearing, and adaptive behavior; cognitive disorders; intellectual deficit). The majority of these pathologies linked to the dysfunction of magnesium-dependent proteins are also associated with the dysfunction of pyridoxine-dependent proteins. An extensive clinical evidence base has been established for the use of Magne B6® in neurology and neuropediatrics.
Conclusion. The combination of organic magnesium salts (citrate, lactate, or pyroglutamate) with vitamin B6 in the Magne B6® product line (Magne B6® Forte, Magne B6® tablets, and Magne B6® oral solution) provides synergistic neuroprotective and mood-stabilizing effects. Evidence-based data confirm the pharmacological efficacy of the original drug Magne B6®.

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