The article is devoted to the study of the effects of isoliquiritigenin in generalized bacterial infections.The aim is to study antibacterial and immunotropic mechanisms and effects of isoliquiritigenin in generalized staphylococcal infections in a mouse model.Materials and methods. To assess the survival rate of Balb/C mice, a generalized infection model caused by Staphylococcus aureus J49 ATCC 25923 with Kaplan-Meier curves was used. The degree of bacteremia during the development of infection was determined by the method of sector crops. The minimum inhibitory concentration of isoliquiritigenin against Staphylococcus aureus J49 ATCC 25923 was determined by serial dilutions methods. To study an antibiofilm activity, the MTT test and atomic force microscopy were used. Immunotropic effects were studied by assessing peptone-induced migration of phagocytes into the abdominal cavity, proliferation of mitogen-activated lymphocytes in the MTT test and their cytokine secretion using the MILLIPLEX MAP kit on a Magpix multiplex analyzer.Results. It has been established that a preliminary intraperitoneal administration of isoliquiritigenin (30 mg/kg) increases the survival rate of Balb/C mice in case of generalized staphylococcal infections. Isoliquiritigenin has antibacterial (MOC = 64 μg/ml) and antibiofilm (4–32 μg/ml) activities against S. aureus J49 ATCC 25923, does not inhibit the migration of phagocytes in the abdominal cavity, dose-dependently inhibits the proliferation and secretion of cytokines by mitogenactivated T-lymphocytes and modulates the production of cytokines (IL-2, IL-12p70, IFNg, TNFα, IL-6, IL-22, IL-23, IL-17A, IL-17F, IL-17E/IL-25, GM-CSF, MIP – 3a/CCL20, IL-10) by the cells of inguinal lymph nodes and splenocytes in the early stages of generalized staphylococcal infections.Conclusion. A preliminary administration of isoliquiritigenin increases the survival rate of mice with generalized staphylococcal infections, which may be associated with both antimicrobial (antistaphylococcal, antibiofilm) and immunotropic mechanisms. The obtained data on the pharmacodynamics of isoliquiritigenin deserve attention from the point of view of the prospects of the new drugs creation that reduce mortality in staphylococcal sepsis.
The results of studying the effect of isoliquiritigenin on animal survival in the model of staphylococcal infection and the function of human and animal phagocytes are presented in this article.The aim of the investigation was to study the effect of an isoliquiritigenin preliminary administration on the survival of animals against the background of staphylococcal infection, as well as on the function of phagocytes in mice and humans.Materials and methods. To assess the survival of Balb/C mice, a model of infection caused by Staphylococcus aureus J49 ATCC 25923 with the construction of Kaplan-Meier curves, was used. The effect on the phagocytes functions was studied by assessing the peptone-induced migration of phagocytes into the abdominal cavity of Balb/C mice, the absorption activity of phagocytes (neutrophils and monocytes) of human blood, as well as their production of reactive oxygen intermediates (ROIs) using а flow cytometry.Results. It was found out that a preliminary triple intraperitoneal administration of isoliquiritigenin (30 mg/kg) increases the survival rate of Balb/C mice in staphylococcal infection caused by Staphylococcus aureus J49 ATCC 25923. At the same time, isoliquiritigenin dose-dependently activates the production of reactive oxygen intermediates by human neutrophils and monocytes without statistically significantly suppressing a phagocytic activity of monocytes and neutrophils against fluoresceinisothiocyanate-labeled S. aureus J 49 ATCC 25923, as well as peptone-induced migration of phagocytes into the abdominal cavity of mice.Conclusion. Thus, a preliminary administration of isoliquiritigenin increases the survival rate of mice with staphylococcal infection and increases the production of reactive oxygen intermediates by phagocytes. The data obtained, can become the basis for further research of antibacterial and immunotropic effects of isoliquiritigenin in order to find new drugs for the treatment of staphylococcal infection.
Представлены сведения об антибактериальных и иммуномодулирующих эффектах флавоноидов. Проанализированы значения минимальных подавляющих концентраций представителей различных классов флавоноидов в отношении патогенов человека. Описаны взаимодействия флавоноидов с антибактериальными лекарственными средствами, а также их влияние на формирование бактериальных биопленок. Представлены сведения о влиянии флавоноидов на некоторые механизмы врожденного и адаптивного иммунитета человека и животных. Приведенные современные литературные данные обосновывают перспективу использования некоторых классов флавоноидов с целью повышения эффективности антимикробной терапии.
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