nnpNeurology, Neuropsychiatry, PsychosomaticsНеврология, нейропсихиатрия, психосоматика2074-27112310-1342"IMA-Press", LLC10.14412/2074-2711-2026-2-108-124nnp-2823Research ArticleEXPERIMENTAL STUDIESЭКСПЕРИМЕНТАЛЬНЫЕ ИССЛЕДОВАНИЯA comparative chemoreactome analysis of choline alfoscerate and ethylmethylhydroxypyridine succinate moleculesСравнительный хемореактомный анализ молекул холина альфосцерата и этилметилгидроксипиридина сукцинатаhttps://orcid.org/0000-0002-7663-710XГромоваО. А.GromovaO. A.

Ольга Алексеевна Громова

119333; ул. Вавилова, 44, корп. 2; Москва; 153012; Шереметевский просп., 8; Иваново

Olga Alekseevna Gromova

119333; 44, Vavilova St., Build. 2; Moscow; 153012; 8, Sheremetyevskiy Prosp.; Ivanovo

unesco.gromova@gmail.comhttps://orcid.org/0000-0002-2659-7998ТоршинИ. Ю.TorshinI. Yu.

119333; ул. Вавилова, 44, корп. 2; Москва

119333; 44, Vavilova St., Build. 2; Moscow

Федеральный исследовательский центр «Информатика и управление» РАН; ФГБОУ ВО «Ивановский государственный медицинский университет» Минздрава РоссииРоссияFederal Research Center “Computer Science and Control”, Russian Academy of Sciences; Ivanovo State Medical University, Ministry of Health of RussiaRussian FederationФедеральный исследовательский центр «Информатика и управление» РАНРоссияFederal Research Center “Computer Science and Control”, Russian Academy of SciencesRussian Federation202624042026182108124Copyright © Gromova O.A., Torshin I.Y., 20262026Громова О.А., Торшин И.Ю.Gromova O.A., Torshin I.Y.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://nnp.ima-press.net/nnp/article/view/2823

   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.

   Сочетанное применение нейропротекторов и ноотропных препаратов с различными механизмами действия является перспективным направлением фармакотерапии снижения концентрации внимания и памяти, хронической ишемии мозга, ишемического инсульта, старческой деменции и др. Проведено сравнительное хемореактомное исследование холина альфосцерата (ХА) и этилметилгидрокспиридина сукцината (ЭМГПС) для выявления молекулярных механизмов синергизма этих молекул на уровне протеома и реактома человека. Оценка выполнялась посредством анализа химических структур ХА и ЭМГПС с использованием современных методов анализа сложных данных (теорий анализа размеченных графов, метрического анализа данных, комбинаторной теории разрешимости, топологической теории анализа плохо формализованных задач), развиваемых в рамках алгебраического подхода к распознаванию. Получены оценки общего воздействия ХА и ЭМГПС на каскады реактома человека и оценки воздействия на конкретные рецепторы протеома человека, обусловливающие общие реактомные эффекты молекул. Для установления общих профилей воздействия ХА и ЭМГПС на реактом человека было проведено исследование эффектов каждой из этих молекул на 255 компонентов реактома, включающих различные сигнальные и метаболические каскады. Степень воздействия на реактом человека была более выражена для ХА (0,62 ± 0,17 у. е.), чем для ЭМГПС (0,54 ± 0,17 у. е.). Хемореактомный анализ изученных молекул с конкретными белками-рецепторами протеома человека включил 1052 таргетных белка (рецепторы различных лигандов: нейротрансмиттеров, гормонов, сигнальных метаболитов и др.). Проведенный анализ показал, что значимые значения констант активации (ЕС50) и ингибирования (IC50) были найдены для 67 белков-рецепторов, из которых активировалось 20 рецепторов и ингибировалось 47 рецепторов. Рецепторы, которые в сопоставимой степени активируются ХА и ЭМГПС, включали каннабиноидный, опиоидный, фарнезоидный и другие рецепторы, что способствует снижению воспаления, боли, улучшает секрецию инсулина и противодействует инсулинорезистентности. Рецепторы, активируемые преимущественно ЭМГПС, оказывают вазорегуляторное, антидепрессивное, анксиолитическое, антидиабетическое и антигипоксантное действие. Ингибирование рецепторов протеома молекулами ХА и ЭМГПС (n = 47) соответствует противовоспалительному, нейропротекторному, противоболевому, инсулин-регулирующему, вазодинамическому, антитромботическому, противоопухолевому эффектам комбинации «ХА + ЭМГПС». Выявленные механизмы реактомного и протеомного действия ХА и ЭМГПС указывают на синергизм комбинации «ХА + ЭМГПС» в нейропротекторном и кардиопротекторном действии. Полученные результаты могут быть отнесены к любым препаратам, действующими началами которых являются ХА и ЭМГПС, при условии одинаковости состава по действующим и вспомогательным веществам.

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The authors declare that there are no conflicts of interest present.