Preview

Neurology, Neuropsychiatry, Psychosomatics

Advanced search

The triple synergy of ethylmethylhydroxypyridine succinate, magnesium, and vitamin B6: Molecular mechanisms

https://doi.org/10.14412/2074-2711-2017-1-42-49

Full Text:

Abstract

Objective: to evaluate the triple effect of ethylmethylhydroxypyridine succinate (EMHPS), organic magnesium salt (magnesium lactate), and vitamin B6 (pyridoxine).

Material and methods. A systematic analysis of the molecular mechanisms of the triple synergic action of EMHPS, magnesium, and vitamin B6 was carried out. For chemoinformational analysis, the investigators developed a new mathematical method based on the combinatorial theory of solvability, which allows one to obtain quantitative estimates of the affinity constants of proteome proteins.

Results. The pharmacological effects of the EMHPS molecule characterized by nootropic and antioxidant properties are shown to work in synergy with magnesium and vitamin B6. A systematic analysis of synergy interactions indicated 46 biological roles, in which the synergy of EMHPS, magnesium, and pyridoxine could be manifested. The main goals of this synergy are to protect neurons from damage, by combating excitotoxicity in the cells and to neutralize excess homocysteine (to reduce the risk of ischemic and thrombotic stroke, myocardial infarction, and coronary heart disease); to improve cognitive functions and neuromuscular transmission, to reduce anxiety, by activating acetylcholine, GABA, and dopamine receptors; to normalize lipid and glucose metabolism, by lowering hyperglycemia and improving the processing of fats.

About the Authors

O. A. Gromova
Ivanovo State Medical Academy, Ministry of Health of Russia
Russian Federation
8, Sheremetevsky Passage., Ivanovo 153000


A. G. Kalacheva
Ivanovo State Medical Academy, Ministry of Health of Russia
Russian Federation
8, Sheremetevsky Passage., Ivanovo 153000


I. Yu. Torshin
Moscow Institute of Physics and Technology
Russian Federation
9, Institutsky Lane, Dolgoprudnyi, Moscow Region 141700


T. R. Grishina
Ivanovo State Medical Academy, Ministry of Health of Russia
Russian Federation
8, Sheremetevsky Passage., Ivanovo 153000


I. K. Tomilova
Ivanovo State Medical Academy, Ministry of Health of Russia
Russian Federation
8, Sheremetevsky Passage., Ivanovo 153000


References

1. Громова ОА, Торшин ИЮ, Федотова ЛЭ, Громов АН. Хемореактомный анализ сукцината этилметилгидроксипиридина. Неврология, нейропсихиатрия, психосоматика. 2016;8(3):53–60. [Gromova OA, Torshin IYu, Fedotova LE, Gromov AN. Chemoreactome analysis of ethylmethylhydroxypyridine succinate. Nevrologiya, neiropsikhiatriya, psikhosomatika = Neurology, Neuropsychiatry, Psychosomatics. 2016;8(3):53–60. (In Russ.)]. doi: 10.14412/2074-2711-2016-3-53-60

2. Громова ОА, Торшин ИЮ, Калачева АГ и др. МексиВ 6 как результат фортификации этилметилгидроксипиридина сукцината магнием и пиридоксином: протеомные эффекты. Неврология, нейропсихиатрия, психосоматика. 2016;8(4):38–44. [Gromova OA, Torshin IYu, Kalacheva AG, et al. MexiB 6 as a result of fortification of ethylmethylhydroxypyridine succinate with magnesium and pyridoxine: proteome effects. Nevrologiya, neiropsikhiatriya, psikhosomatika = Neurology, Neuropsychiatry, Psychosomatics. 2016;8(4):38–44. (In Russ.)]. doi: 10.14412/2074-2711-2016-4-38-44

3. Громова ОА, Калачева АГ, Торшин ИЮ и др. Недостаточность магния – достоверный фактор риска коморбидных состояний: результаты крупномасштабного скрининга магниевого статуса в регионах России. Фарматека. 2013;(6):115–29. [Gromova OA, Kalacheva AG, Torshin IYu, et al. Deficiency of magnesium – a significant risk factor of comorbid conditions: results of a large-scale screening of magnesium status in the regions of Russia. Farmateka. 2013;(6):115–29. (In Russ.)].

4. Громова ОА, Торшин ИЮ, Лиманова ОА, Гоголева ИВ. Анализ взаимосвязи между обеспеченностью магнием и риском соматических заболеваний у россиянок 18–45 лет методами интеллектуального анализа данных. Эффективная фармакотерапия. Акушерство и Гинекология. 2014;(2):10-23. [Gromova OA, Torshin IYu, Limanova OA, Gogoleva IV. Analysis of the relationship between the availability of magnesium and risk of somatic diseases in women 18–45 years with data mining methods. Effective pharmacotherapy. Akusherstvo i Ginekologiya. 2014;(2):10-23. (In Russ.)].

5. Torshin IYu. On metric spaces arising during formalization of problems of recognition and classification. Part 2: density properties. Pattern Recognition and Image Analysis 2016 July;26(3): 483-496. doi: 10.1134/S1054661816030202

6. Torshin IYu. Sensing the change from molecular genetics to personalized medicine. New York: Nova Biomedical Books; 2009.

7. Zhang C, Messing A, Chiu S. Specific alteration of spontaneous GABAergic inhibition in cerebellar purkinje cells in mice lacking the potassium channel Kv1. 1. J Neurosci. 1999 Apr 15;19(8):2852-64.

8. Campbell V, Berrow N, Fitzgerald E, et al. Inhibition of the interaction of G protein G(o) with calcium channels by the calcium channel beta-subunit in rat neurones. J Physiol. 1995 Jun 1;485 ( Pt 2):365-72.

9. Bender A, Beavo J. Cyclic nucleotide phosphodiesterases: molecular regulation to clinical use. Pharmacol Rev. 2006 Sep;58(3):488-520.

10. Zhang X, Feng Z, Chergui K. Allosteric modulation of GluN2C/GluN2D-containing NMDA receptors bidirectionally modulates dopamine release: implication for Parkinson's disease. Br J Pharmacol. 2014 Aug;171(16): 3938-45. doi: 10.1111/bph.12758.

11. Solomons N. Trace elements in nutrition of the elderly. 1. Established RDAs for iron, zinc, and iodine. Postgrad Med. 1986 May 1;79(6): 231-2, 235-6, 238-9 passim.

12. Hvas AM, Juul S, Bech P, Nexo E. Vitamin B6 level is associated with symptoms of depression. Psychother Psychosom. 2004 Nov-Dec; 73(6):340-3.

13. Malouf R, Grimley Evans J. The effect of vitamin B6 on cognition. Cochrane Database Syst Rev. 2003;(4):CD004393.

14. Ferreira DD, Stutz B, de Mello FG, et al. Caffeine potentiates the release of GABA mediated by NMDA receptor activation: Involvement of A1 adenosine receptors. Neuroscience. 2014 Dec 5;281:208-15. doi: 10.1016/j.neuroscience.2014.09.060. Epub 2014 Oct 5.

15. Palee S, Apaijai N, Shinlapawittayatorn K, et al. Acetylcholine Attenuates Hydrogen Peroxide-Induced Intracellular Calcium Dyshomeostasis Through Both Muscarinic and Nicotinic Receptors in Cardiomyocytes. Cell Physiol Biochem. 2016;39(1):341-9. doi: 10.1159/000445628. Epub 2016 Jun 29.

16. Dorszewska J, Florczak J, Rozycka A, et al. Polymorphisms of the CHRNA4 gene encoding the alpha4 subunit of nicotinic acetylcholine receptor as related to the oxidative DNA damage and the level of apoptotic proteins in lymphocytes of the patients with Alzheimer's disease. DNA Cell Biol. 2005 Dec;24(12):786-94.

17. Stegemann A, Bohm M. The alpha7 nicotinic acetylcholine receptor agonist tropisetron counteracts UVA-mediated oxidative stress in human dermal fibroblasts. Exp Dermatol. Exp Dermatol. 2016 Dec;25(12):994-996. doi: 10.1111/exd.13220.

18. Gao Z, Zhang H, Liu J, et al. Cyclooxygenase-2-dependent oxidative stress mediates palmitate-induced impairment of endothelium-dependent relaxations in mouse arteries. Biochem Pharmacol. 2014 Oct 15;91(4):474-82. doi: 10.1016/j.bcp.2014.08.009. Epub 2014 Aug 19.

19. Chang T, Jeong W, Woo H, et al. Characterization of mammalian sulfiredoxin and its reactivation of hyperoxidized peroxiredoxin through reduction of cysteine sulfinic acid in the active site to cysteine. J Biol Chem. 2004 Dec 3;279(49):50994-1001. Epub 2004 Sep 24.

20. Wang X, Guo J, Fei E, et al. BAG5 protects against mitochondrial oxidative damage through regulating PINK1 degradation. PLoS One. 2014 Jan 24;9(1):e86276. doi: 10.1371/journal.pone.0086276. eCollection 2014.

21. Sengupta S, Tu S, Wedin K, et al. Interactions with WNK (with no lysine) family members regulate oxidative stress response 1 and ion co-transporter activity. J Biol Chem. 2012 Nov 2;287(45):37868-79. doi: 10.1074/jbc.M112.398750. Epub 2012 Sep 18.

22. Abousaab A, Warsi J, Elvira B, et al. Down-Regulation of Excitatory Amino Acid Transporters EAAT1 and EAAT2 by the Kinases SPAK and OSR1. J Membr Biol. 2015 Dec;248(6):1107-19. doi: 10.1007/s00232-015-9826-5. Epub 2015 Aug 2.

23. Pombo C, Bonventre J, Molnar A, et al. Activation of a human Ste20-like kinase by oxidant stress defines a novel stress response pathway. EMBO J. 1996 Sep 2;15(17):4537- 46. 24. De Pra SD, Ferreira GK,

24. Carvalho-Silva M, et al. L-tyrosine induces DNA damage in brain and blood of rats. Neurochem Res. 2014 Jan;39(1):202-7. doi: 10.1007/s11064-013-1207-9. Epub 2013 Dec 3.

25. Torshin IY, Gromova OA. Magnesium and pyridoxine: fundamental studies and clinical practice. New York: Nova Science Publ.; 2011. 196 p.

26. Скворцова ВИ, Стаховская ЛВ, Нарциссов ЯР и др. Рандомизированное двойное слепое плацебо-контролируемое исследование эффективности и безопасности мексидола в комплексной терапии ишемического инсульта в остром периоде. Инсульт. 2006;(18):47-54. [Skvortsova VI, Stakhovskaya LV, Nartsissov YaR, et al. Randomized, doubleblind, placebo-controlled study of the efficacy and safety of Mexidol in complex therapy of ischemic stroke in the acute period. Insul't. 2006;(18):47-54. (In Russ.)].


For citation:


Gromova O.A., Kalacheva A.G., Torshin I.Y., Grishina T.R., Tomilova I.K. The triple synergy of ethylmethylhydroxypyridine succinate, magnesium, and vitamin B6: Molecular mechanisms. Neurology, Neuropsychiatry, Psychosomatics. 2017;9(1):42-49. (In Russ.) https://doi.org/10.14412/2074-2711-2017-1-42-49

Views: 241


Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.


ISSN 2074-2711 (Print)
ISSN 2310-1342 (Online)