Oleuropein reduces LPS-induced inflammation via stimulating M2 macrophage polarization

Biomed Pharmacother. 2023 Jul:163:114857. doi: 10.1016/j.biopha.2023.114857. Epub 2023 May 11.

Abstract

Oleuropein (OLEU) is the most prevalent phenolic component in olive varieties, and it has been considered for its powerful antioxidant properties in therapeutic applications. OLEU has anti-inflammatory properties and performs this property by suppressing inflammatory cells' function and reducing oxidative stress caused by various factors. This study investigated the ability of OLEU to polarize LPS-stimulated murine macrophage (MQ) cell RAW 264.7 into M1/M2 macrophages. As a first step, the cytotoxicity effects of OLEU were evaluated on LPS-stimulated RAW 264.7 cells using the thiazolyl blue (MTT) colorimetric test. Then, cytokines production, gene expression (Real-Time PCR), and functions (Nitrite oxide assay and phagocytosis assay) of OLEU-treated LPS-stimulated RAW 264.7 cells were evaluated. Our findings demonstrated that OLEU could reduce nitrite oxide (NO) production in LPS-stimulated RAW 264.7 cells by downregulating the inducible nitric oxide synthase gene expression. Furthermore, OLEU therapy decreases the expression of M1-associated pro-inflammatory cytokines production (IL-12, IFN-γ, and TNF-α) and genes expression (iNOS, TNF-α) while increasing the M2-associated anti-inflammatory gene expression and cytokines production (IL-10, and TGF-β). Based on the result, OLEU may be considered a potential therapeutic approach for inflammatory diseases due to its possible effects on oxidative stress-related factors, cytokine expression and production, and phagocytosis.

Keywords: Anti-inflammatory cytokines; Inflammation; LPS; M2 macrophage; Oleuropein; Pro-inflammatory cytokines.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / therapeutic use
  • Cytokines / metabolism
  • Inflammation / chemically induced
  • Inflammation / drug therapy
  • Inflammation / genetics
  • Lipopolysaccharides* / adverse effects
  • Macrophages / metabolism
  • Mice
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase Type II / metabolism
  • Nitrites / metabolism
  • RAW 264.7 Cells
  • Tumor Necrosis Factor-alpha* / metabolism

Substances

  • Lipopolysaccharides
  • oleuropein
  • Tumor Necrosis Factor-alpha
  • Nitrites
  • Cytokines
  • Anti-Inflammatory Agents
  • Nitric Oxide Synthase Type II
  • Nitric Oxide