Effects ofcis-resveratrol on inflammatory murine macrophages: antioxidant activity and down-regulation of inflammatory genes

Abstract
This study investigated for the first time the effects of the cis isomer of resveratrol (c-RESV) on the responses of inflammatory murine peritoneal macrophages, namely on the production of reactive oxygen species (ROS) and reactive nitrogen species (RNS) during the respiratory burst; on the biosynthesis of other mediators of inflammation such prostaglandins; and on the expression of inflammatory genes such as inducible nitric oxide synthase (NOS)-2 and inducible cyclooxygenase (COX)-2. Treatment with 1–100 μM c-RESV significantly inhibited intracellular and extracellular ROS production, and c-RESV at 10–100 μM significantly reduced RNS production. c-RESV at 1–100 μM was ineffective for scavenging superoxide radicals (O2•−), generated enzymatically by a hypoxanthine (HX)/xanthine oxidase (XO) system and/or for inhibiting XO activity. However, c-RESV at 10–100 μM decreased nicotinamide adenine dinucleotide/nicotinamide adenine dinucleotide phosphate (NADH/NADPH) oxidase activity in macrophage homogenates. c-RESV at 100 μM decreased NOS-2 and COX-2 mRNA levels in lipopolysaccharide (LPS) interferon gamma (IFN-γ)-treated macrophages. At 10–100 μM, c-RESV also significantly inhibited NOS-2 and COX-2 protein synthesis and decreased prostaglandin E2 (PGE2) production. These results indicate that c-RESV at micromolar concentrations significantly attenuates several components of the macrophage response to proinflammatory stimuli (notably, production of O2•− and of the proinflammatory mediators NO and PGE2).
Funding Information
  • Comisión Interministerial de Ciencia y Tecnología (SAF2000-0137, SAF2002-02645)
  • Consellería de Educación e Ordenación Universitaria, Xunta de Galicia (PGIDIT02BTF20301PR, PGIDIT02PXIC20305PN)
  • Almirall Prodesfarma Laboratories