Studying the hypolypidemic activity of flavonoids and isoflavonoids of the Ononis arvensis L. Methods by in silico

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Abstract

Introduction. Today, one of the reliably known causes of mortality in the Russian Federation is diseases of the cardiovascular system, a significant part of which is associated with atherosclerotic disease. Combination therapy for diseases of the cardiovascular system includes, among other things, the use of modern lipid-lowering drugs, the use of which is often limited due to their pronounced side effects. In this regard, it seemed appropriate to search for new compounds of natural origin that potentially have lipid-lowering activity with minimal side effects. According to the scientific literature, natural phenolic compounds, namely substances from the group of flavonoids and isoflavonoids, have a set of such characteristics. In this regard, steelgrass (Ononis arvensis L.), the chemical composition of which is extremely rich and diverse in terms of flavonoids and isoflavonoids, can be a rather promising source for searching and screening compounds with a given activity.

The aim of the study. The purpose of the work was to study and predict the hypolipidemic activity of flavonoids and isoflavonoids of Ononis arvensis L. using in silico methods.

Material and methods. The objects of the study were the structural formulas of flavonoids and isoflavonoids of field steelhead. Calculation of molecular properties was carried out using the Molinspiration chemoinformatic software. Computer prediction of lipid-lowering activity was carried out using the PASS-online service. Molecular docking was performed using the CB-Dock2 services for blind docking and Webina 1.0.5 for active site docking. Hepatotoxicity, mutagenicity and cytotoxicity of the analyzed biologically active substances were studied using the ProTox-II resource.

Results. As a result of in silico studies, it was found that most of the studied flavonoids and isoflavonoids correspond to the Lipinski rule and the drug-likeness concept. In addition, for all studied biologically active substances, activities associated with a decrease in lipid fractions in the body were predicted. The results of molecular docking indicate that all analyzed compounds are capable of potentially inhibiting the enzyme HMG-CoA reductase, which makes it possible to predict the required lipid-lowering effect. Studying the toxicity of the research objects, most of them in silico demonstrated a high level of safety.

Conclusions. The prospects for further research on the development of targeted technology for obtaining herbal preparations from steelhead, enriched with flavonoids and isoflavonoids, as well as subsequent tests to confirm hypolipidemic activity in in vitro and in vivo experiments are shown.

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About the authors

N. А. Davitavyan

Kuban State Medical University

Author for correspondence.
Email: pharmdep@ksma.ru

Ph.D. (Pharm.), Associate Professor, Associate Professor of the Pharmaceutics Department

Russian Federation, Krasnodar

Е. B. Nikiforova

Kuban State Medical University

Email: pharmdep@ksma.ru

Ph.D. (Pharm.), Associate Professor, Head of the Pharmaceutics Department

Russian Federation, Krasnodar

Y. А. Pogulyay

Kuban State Medical University

Email: pharmdep@ksma.ru

Student, the Pharmaceutics Department

Russian Federation, Krasnodar

М. R. Khochava

Kuban State Medical University

Email: pharmdep@ksma.ru

Ph.D. (Pharm.), Associate Professor, Associate Professor of the Pharmaceutics Department

Russian Federation, Krasnodar

P. G. Mizina

All-Russian Scientific Research Institute of Medicinal and Aromatic Plants

Email: mizina-pg@yandex.ru

Dr.Sc. (Pharm.), Professor, Adviser

Russian Federation, Moscow

G. V. Adamov

All-Russian Scientific Research Institute of Medicinal and Aromatic Plants

Email: grig.adamov@mail.ru

Ph.D. (Pharm.), Liding Research Scientist, Department of Chemistry of Natural Compounds

Russian Federation, Moscow

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Supplementary files

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2. Fig. 1. Schematic representation of the proposed interaction of trifolirizine with the active center of HMG-CoA reductase: A – The docking position; B – Interaction with amino acid residues

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3. Fig. 2. Schematic representation of the proposed interaction of ononin with the active center of HMG-CoA reductase: A - Docking position; B – Interaction with amino acid residues

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4. Fig. 3. Schematic representation of the proposed interaction of rosuvastatin with the active center of HMG-CoA reductase: A – Docking position; B - Interaction with amino acid residues

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