The influence of Salvia cadmica Boiss. extracts on the M1/M2 polarization of macrophages primed with Helicobacter pylori lipopolysaccharide in conjunction with NF-kappa B activation, production of cytokines, phagocytic activity and total DNA methylation

Ethnopharmacological relevance: The large number of secondary derivatives have been isolated from the genus Salvia with about 700 species, and used in the pharmacopoeia throughout the world. Various biological prop-erties of Salvia formulations have been reported including as antioxidant, antimicrobial, hypotensive, anti -hyperglycemia, anti-hyperlipidemia, anti-cancer, and skin curative. Salvia cadmica Boiss. root and aerial part extracts enriched with polyphenols are bactericidal towards gastric pathogen Helicobacter pylori (Hp) and diminish deleterious effects induced by Hp lipopolysaccharide (LPS) towards gastric epithelial cells.Aim of this study: To examine the influence of S. cadmica extracts on the M1/M2 polarization of macrophages primed with Hp LPS vs standard LPS Escherichia coli (Ec), and the macrophage cytokine as well as phagocytic activity, which are affected during Hp infection. Material and methods: Macrophages derived from THP-1 human monocytes primed with LPS Hp/Ec and/or S. cadmica extracts, were examined for the biomarkers of activation (surface, cytoplasmic or soluble), and phagocytic capacity. The bone marrow macrophages of Cavia porcellus were used to determine the engulfment of Hp. Results: Priming of THP-1 cells (24h) with LPS Hp/Ec resulted in polarization of M1 macrophages, activation of nuclear factor kappa B, secretion of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1 beta, macrophage chemotactic protein (MCP)-1, immunoregulatory IL-10, and production of reactive oxygen species. These effects were diminished after restimulation of cells with S. cadmica extracts. THP-1 macrophages exposed to studied extracts showed an increased phagocytic capacity, in conjunction with elevated CD11b/CD11d expression and enhanced production of inducible nitric oxide synthase. They also increased Hp engulfment by bone marrow macrophages. These effects were not related to a global DNA methylation.Conclusions: S. cadmica extracts possess an immunomodulating activity, which might be useful in control of H. pylori LPS driven activity of macrophages.