Immunobiological efficacy of a new sodium polyprenyl phosphate based medicine for the treatment and prevention of experimenrtal metabolic syndrome

Abstract

The aim of the research was to study the population composition of the splenic lymphoid cells, to assess the functional activity of lymphocytes as well as the state of the gastrointestinal tract microbiota in experimental modeling of metabolic syndrome (MS).The studies were conducted using two experimental models of MS and hyperlipidemia (HL), based on prolonged drinking of animals with 20% aqueous fructose solution with added cholesterol and intraperitoneal administration of Poloxamer 407 to mice, respectively.The results of the experiments indicate a change in the population composition of splenocytes (decrease in CD4+ and CD8+T cells, activation of CD4+CD25+FoxP3+Thed cells), accompanied by a decrease in T cell activity and increased proliferation of B lymphocytes, impaired production of IL-15 and IL-22, as well as lipid and carbohydrate metabolism (adiponectin, leptin, insulin), which serves as a prerequisite for the development of chronic inflammation, which is a pathogenetic sign of MS.We found changes in the intestinal microbiota of mice characteristic of the manifestation of metabolic dysbiosis – an increase in the representation of Firmicutes bacteria (staphylococci, streptococci, enterococci) in the biomaterial, changes in the content of facultative (E. coli) and transient (Enterobacter) microflora.In order to develop a new kind of medicine for therapy and prevention of HL and MS, we used a combination of sodium polyprenyl phosphate (PP) and beta-sitosterol (BSS), polyisoprenoid derivatives of plant origin.More pronounced changes were found in the splenocyte population composition and activation parameters of Treg cells in HL modeling compared with the MS model. The introduction of PP and BSS has an immunocorrective effect during treatment.The therapeutic effect of this drug, as well as the prevention of the MS symptoms, is accompanied by normalization of the microbiota state.The data obtained indicate the prospects of using PP and BSS for the prevention and treatment of HL and MS in order to influence the leading links in the pathogenesis of metabolic disease.

Keywords

• metabolic syndrome
• experimental models
• immune response
• gut microbiota
• sodium polyprenyl phosphate