Antibacterial and immunotropic properties of isoliquiritigenin in generalized staphylococcal infection in mice

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Abstract

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 mitogen-activated 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.

About the authors

Elena A. Solyonova

Chuvash State University named after I.N. Ulyanov

Author for correspondence.
Email: elensoul@mail.ru
ORCID iD: 0000-0001-6104-0864

Junior Researcher, Department of Pharmacology, Clinical Pharmacology and Biochemistry

Russian Federation, 15, Moskovsky prospect, Cheboksary, Chuvash Republic, 428015

Svetlana I. Pavlova

Chuvash State University named after I.N. Ulyanov

Email: flavonoid@yandex.ru
ORCID iD: 0000-0001-9976-7866

Doctor of Sciences (Medicine), the Head of the Department of Pharmacology, Clinical Pharmacology and Biochemistry

Russian Federation, 15, Moskovsky prospect, Cheboksary, Chuvash Republic, 428015

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Supplementary files

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1. JATS XML
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2. Figure 1 – Survival of Balb/C mice (males) infected with S. aureus J49 ATCC 25923

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3. Figure 2 – Effect of ISL on the growth of S. aureus J49 ATCC 25923

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4. Figure 3 – Effect of ISL on biofilm formation of S. aureus J49 ATCC 25923

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5. Figure 4 – Dynamics of splenocytes (A) and inguinal lymph node cells (B) in the model of Balb/C mice staphylococcal infection

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6. Figure 5 – Effect of preliminary ISL administration on the levels of cytokines (groups Th-1 and IL-10) produced by the cells of the inguinal lymph nodes of Balb/C mice infected with S. aureus J49 ATCC 25923 (5×108 CFUs/mouse) (* p<0.05)

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7. Figure 6 – Effect of preliminary ISL administration on the levels of cytokines (Th-17 group) produced by the cells of the inguinal lymph nodes of Balb/C mice infected with S. aureus J49 ATCC 25923 (5×108 CFUs/mouse) (* p<0.05)

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8. Figure 7 – Effect of preliminary ISL administration on cytokine levels (groups Th-1 and IL-10) produced by splenocytes of Balb/C mice infected with S. aureus J49 ATCC 25923 (5×108 CFUs/mouse, intraperitoneal) (* p<0.05)

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9. Figure 8 – Effect of preliminary ISL administration on cytokine levels (group Th-17), produced by splenocytes of Balb/C mice infected with S. aureus J49 ATCC 25923 (5×108 CFUs/mouse, intraperitoneally) (*p<0.05)

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Copyright (c) 2020 Solyonova E.A., Pavlova S.I.

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