Anti-Inflammatory Properties of Metformin During Cultivation of Primary Rat Astrocytes in a Medium with High Glucose Concentration

Investigation of the relationship between inflammation and energy metabolism is important for understanding biology of chronic noncommunicable diseases. Use of metformin, a drug for treatment of diabetes, is considered as a promising direction for treatment of neurodegenerative diseases and other neuropathologies with an inflammatory component. Astrocytes play an important role in the regulation of energy metabolism and neuroinflammation; therefore, we studied the effect of metformin on the cellular responses of primary rat astrocytes cultured in a medium with high glucose concentration (22.5 mM, 48-h incubation). Lipopolysaccharide (LPS) was used to stimulate inflammation. The effects of metformin were assessed by monitoring changes in the expression of proinflammatory cytokines and synthesis of oxylipins, assayed with ultra-high-performance liquid chromatography and tandem mass spectrometry (UPLC-MS/MS). Changes at the intracellular level were assessed by analyzing phosphorylation of ERK kinase and transcription factor STAT3, as well as enzymes mediating oxylipin synthesis, cyclooxygenase 1 and 2 (COX). It was found that, independent on glucose concentration, metformin reduced the LPS-stimulated release of cytokines IL-1β and IL-6, decreased activity of the transcription factor STAT3, ERK kinase, synthesis of the derivatives of the cyclooxygenase branch of metabolism of oxylipins and anandamide, and did not affect formation of ROS. The study of energy phenotype of the cells showed that metformin activated glycolysis and inhibited mitochondrial respiration and oxidative phosphorylation, independent on LPS stimulation and cell cultivation at high glucose concentration. Thus, it has been shown that metformin exhibits anti-inflammatory effects, and its effect on the synthesis of cytokines, prostaglandins, and other lipid mediators could determine beneficial effects of metformin in models of neuropathology.

Авторы
Gorbatenko V.O.1 , Goriainov S.V. 2 , Babenko V.A.3 , Plotnikov E.Y.3 , Sergeeva M.G. 3 , Chistyakov D.V. 3
Журнал
Номер выпуска
7
Язык
Английский
Страницы
577-589
Статус
Опубликовано
Том
87
Год
2022
Организации
  • 1 Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University
  • 2 Peoples’ Friendship University of Russia (RUDN University)
  • 3 Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University
Ключевые слова
astrocytes; hyperglycemia; cytokines; oxylipins; Stat3; Erk; ros; polyunsaturated fatty acids; anandamide; metformin
Дата создания
28.12.2023
Дата изменения
28.12.2023
Постоянная ссылка
https://repository.rudn.ru/ru/records/article/record/100130/
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