The flavonoid rutin modulates microglial/macrophage activation to a CD150/CD206 M2 phenotype

Chem Biol Interact. 2017 Aug 25:274:89-99. doi: 10.1016/j.cbi.2017.07.004. Epub 2017 Jul 8.

Abstract

Rutin is a glycosylated flavonoid present in many fruits and plants that has been demonstrated to have anti-inflammatory and antioxidant properties. However, little is known about the mechanisms underlying microglial activation and its effects on the regulation of cytokines and chemokines associated with inflammatory responses in the central nervous system. In this study we examined the effect of rutin on resting or lipopolysaccharide (LPS)-stimulated microglia and characterized their modulation to an activated M1 phenotype or an alternatively activated M2 phenotype. Microglial cells were treated with rutin (1-100 μM); alternatively, microglial cells were stimulated with LPS and the cells were then treated with rutin (50 μM). The results revealed that rutin treatment was not toxic to microglial cells and induced a dose-dependent increase in microglial proliferation associated with changes in morphology after 24 h of treatment. Rutin also induced microglial activation characterized by an increase in OX-42 positive cells and a large proportion of cells with a CD150/CD206-positive M2 phenotype. Rutin also induced a decrease in the mRNA levels of TNF, IL1β, IL6 and iNOS, reduced the production of IL6, TNF, and nitric oxide, and increased production of the M2 regulatory cytokine IL10 and arginase. Rutin also significantly inhibited the LPS-induced expression of PTGS2, IL18 and TGFβ mRNA. These findings show that rutin has the ability to promote microglial proliferation and induces microglial polarization to the M2 profile when cells are stimulated with LPS. These results point this flavonoid as a possible alternative in the treatment or prevention of neurodegenerative disorders.

Keywords: Flavonoid; LPS arginase; M2 (CD150/CD206) phenotype; Microglia; Rutin.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / chemistry
  • Anti-Inflammatory Agents / pharmacology*
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Cyclooxygenase 2 / metabolism
  • Cytokines / analysis
  • Flavonoids / chemistry
  • Flavonoids / pharmacology
  • Interleukin-18 / genetics
  • Interleukin-18 / metabolism
  • Lectins, C-Type / metabolism*
  • Lipopolysaccharides / toxicity
  • Macrophage Activation / drug effects
  • Macrophages / cytology
  • Macrophages / drug effects
  • Macrophages / metabolism
  • Mannose Receptor
  • Mannose-Binding Lectins / metabolism*
  • Microglia / cytology
  • Microglia / drug effects*
  • Microglia / metabolism
  • Nitric Oxide / metabolism
  • Phenotype
  • Rats
  • Rats, Wistar
  • Receptors, Cell Surface / metabolism*
  • Rutin / chemistry
  • Rutin / pharmacology*
  • Signaling Lymphocytic Activation Molecule Family Member 1 / metabolism*
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta / metabolism

Substances

  • Anti-Inflammatory Agents
  • Cytokines
  • Flavonoids
  • Interleukin-18
  • Lectins, C-Type
  • Lipopolysaccharides
  • Mannose Receptor
  • Mannose-Binding Lectins
  • Receptors, Cell Surface
  • Transforming Growth Factor beta
  • Signaling Lymphocytic Activation Molecule Family Member 1
  • Nitric Oxide
  • Rutin
  • Cyclooxygenase 2