Chemotranscriptome analysis of synergism between D-chiroinositol and myoinositol in the context of postgenomic pharmacology


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Abstract

Background: The effect of myoinositol (MI) and D-chiroinositol (DCI) on gene transcription is of great importance for assessing the molecular mechanisms of synergism between these micronutrients. Such micronutrients are necessary for the prevention of insulin resistance, manifestations of polycystic ovary syndrome, congenital malformations and fetal macrosomia, especially in pregnant women with insulin resistance, dyslipidemia, and overweight. Materials and methods: The paper presents the results of a chemotranscriptome analysis of the effects of myoinositol (MI) and D-chiroinositol (DCI). The dose-dependent effects of MI and DCI on the transcription of 12716 annotated human genes in human umbilical vein endothelial cells (HUVEC line, stimulation of cells with MI/DCI at 6 different concentrations for 24 h) were evaluated. Results: MI was found to cause significant transcription changes (more than 50% per 10 pmol on average) of 6516 genes: the expression of 4085 genes increased, and the expression of 2431 genes decreased. DCI is an important MI synergist in six functional groups of genes: (1) fat metabolism, (2) carbohydrate metabolism, (3) thyroid function, (4) morphogenesis, cell differentiation and survival, (5) neuroprotection and neurotrophicity, (6) structure and function of blood vessels. MI and DCI changed the expression of genes involved in the human body’s response to 49 drugs. Conclusion: It was possible to establish an individual pattern of DCI and MI action and to identify the molecular mechanisms of synergism between these two forms of inositol at the level of the human transcriptome. The results of the study suggest a higher efficiency of the combined administration of MI and DCI for the correction of disorders of carbohydrate and fat metabolism in pregnant women and for the prevention of abnormal fetal morphogenesis.

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About the authors

Ivan Yu. Torshin

Institute of Pharmacoinformatics, Federal Research Center «Informatics and Management», Russian Academy of Sciences

PhD in Applied Mathematics

Olga A. Gromova

Institute of Pharmacoinformatics, Federal Research Center «Informatics and Management», Russian Academy of Sciences

Email: unesco.gromova@gmail.com
Dr. Med. Sci., Professor

Nana K. Tetruashvili

Academician V.I. Kulakov National Medical Research Centre for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Email: n_tetruashvili@oparina4.ru
Dr. Med. Sci., Head of the 2nd Obstetrics Department of Pathology of Pregnancy

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