medsovetМедицинский СоветMeditsinskiy sovet = Medical Council2079-701X2658-5790REMEDIUM GROUP Ltd.10.21518/ms2024-116medsovet-8187Research ArticleНЕРВНО-ПСИХИЧЕСКИЕ РАССТРОЙСТВАNEUROPSYCHIATRIC DISORDERSФармакоинформационный, геронтоинформационный и хемореактомный анализ молекулы цитруллина малата, карнитина, сульбутиамина и мельдония для выявления молекулярных механизмов антиастенического действияPharmacoinformational, gerontoinformational and chemoreactomic analysis of the molecule of citrulline malate, carnitine, sulbutiamine and meldonium to identify the molecular mechanisms of antiasthenic actionhttps://orcid.org/0000-0002-2659-7998ТоршинИ. Ю.TorshinI. Yu.

Торшин Иван Юрьевич, к.ф-м.н., к.х.н., ведущий научный сотрудник

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

Scopus Author ID: 7003300274

Researcher ID: C-7683-2018

Ivan Yu. Torshin, Cand. Sci. (Physcal. and Mathem.), Cand. Sci. (Chem.), Leading Researcher

44, Bldg. 2, Vavilov St., Moscow, 119333

https://orcid.org/0000-0002-7663-710XГромоваО. А.GromovaO. A.

Громова Ольга Алексеевна, д.м.н., профессор, ведущий научный сотрудник

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

Olga A. Gromova, Dr. Sci. (Med.), Professor, Leading Researcher

44, Bldg. 2, Vavilov St., Moscow, 119333

unesco.gromova@gmail.comФедеральный исследовательский центр «Информатика и управление» Российской академии наукРоссияFederal Research Center “Computer Science and Control” of the Russian Academy of SciencesRussian Federation202402052024037079Copyright © Торшин И.Ю., Громова О.А., 20242024Торшин И.Ю., Громова О.А.Torshin I.Y., Gromova O.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.med-sovet.pro/jour/article/view/8187

Патофизиология астении весьма сложна и связана с хронической болезнью почек, сердечной недостаточностью, хронической обструктивной болезнью легких, саркопенией, бактериальными и вирусными патогенами, микронутриентным дисбалансом питания, гипотиреозом и др. Астения может возникать при чрезмерных (для данного пациента) физических, психических или умственных нагрузках и нарушениях адаптации или носить ятрогенный характер (в частности, вследствие приема лекарств, способствующих усиленным потерям витаминов и микроэлементов), в т. ч. вследствие нежелательных взаимодействий лекарств. Сложный характер патофизиологии астении обуславливает необходимость применения дифференцированного подхода, направленного на устранение основной причины астении у данного пациента. В случае если астения связана, прежде всего, с нарушениями энергетического метаболизма, то патофизиологическим лечением является применение нутриентов, поддерживающих внутриклеточный синтез, таких как цитруллин, цитруллина малат, основными механизмами действия которых является поддержка цикла мочевины, усиление выведения ионов аммония, снижение концентрации лактата в крови. В работе представлены результаты сравнительного фармакоинформационного и хемореактомного анализа цитруллина, цитруллина малата (ЦМ), карнитина, сульбутиамина и мельдония. Профиль фармакологических эффектов цитруллина/ЦМ существенно отличался от профилей других молекул. Для цитруллина/ЦМ выявлены холинергические, антидепрессантные, липид-модифицирующие эффекты и предположено антиастеническое действие при использовании в терапии мышечной дистрофии Дюшенна и при нарушениях углеводного обмена. В отличие от других молекул ЦМ и карнитин не способствуют потерям витаминов и минералов. Ингибирование ЦМ рецептора серотонина 5HT3A может улучшать вестибуляцию, т. к. блокаторы 5-НТ3-рецепторов, концентрирующихся в нейронах вестибулярного аппарата, улучшают тесты на равновесие, ходьбу в эксперименте у мышей. Показано положительное дозозависимое действие цитруллина и ЦМ на продолжительность жизни ряда модельных организмов. Хемореактомный анализ белков-рецепторов молекул указал на новые молекулярные механизмы антиастенического действия ЦМ: ингибирование рецепторов серотонина, сенсорного белка-рецептора кальция, рецепторов хемокинов, липополисахаридов (толл-рецепторов), ноцицептина, глутамата, орексина, пуринов и простаноидов, биосинтез NF-kB и ФНОα.

The pathophysiology of asthenia is very complex and is associated with chronic kidney disease, heart failure, chronic obstructive pulmonary disease, sarcopenia, bacterial and viral pathogens, micronutrient nutritional imbalances, hypothyroidism, etc. Asthenia can occur with excessive (for a given patient) physical, mental or mental stress and adaptation disorders or be iatrogenic in nature (in particular, due to taking medications that contribute to increased loss of vitamins and microelements), incl. due to unwanted drug interactions. The complex nature of the pathophysiology of asthenia necessitates the use of a differentiated approach aimed at eliminating the main cause of asthenia in a given patient. If asthenia is associated primarily with disorders of energy metabolism, then the pathophysiological treatment is the use of nutrients that support intracellular synthesis - such as citrulline, citrulline malate, the main mechanisms of action of which are supporting the urea cycle, increasing the excretion of ammonium ions, reducing the concentration lactate in the blood. The paper presents the results of a comparative pharmacoinformatic and chemoreactomic analysis of citrulline, citrulline malate (CM), carnitine, sulbutiamine and meldonium. The profile of pharmacological effects of citrulline/CM was significantly different from the profiles of other molecules. For citrulline/CM, cholinergic, antidepressant, and lipid-modifying effects have been identified and an antiasthenic effect has been suggested when used in the treatment of Duchenne muscular dystrophy and for disorders of carbohydrate metabolism. Unlike other molecules, CM and carnitine do not contribute to the loss of vitamins and minerals. Inhibition of the CM serotonin 5HT3A receptor may improve vestibulation because blockers of 5-HT3 receptors concentrated in neurons of the vestibular apparatus, improves tests of balance and walking in an experiment in mice. A positive dose-dependent effect of citrulline and CM on the lifespan of a number of model organisms has been shown. Chemoreactomic analysis of molecular receptor proteins indicated new molecular mechanisms of the antiasthenic action of CM: inhibition of serotonin receptors, calcium sensor protein receptors, chemokine receptors, lipopolysaccharides (toll receptors), nociceptin, glutamate, orexin, purines and prostanoids, biosynthesis of NF-kB and TNFα.

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