Inhibition of inducible nitric oxide synthase by Acanthopanax senticosus extract in RAW264.7 macrophages

Abstract

Aim of the study: The herb Acanthopanax senticosus (Siberian ginseng) has long been used as a traditional medicine. However, little is known about anti-inflammatory effects and its mechanisms of action. Excess production of nitric oxide (NO) is one of the characteristics of inflammation. In this study we examined the effects of A. senticosus extract (ASE) on NO production and inducible nitric oxide synthase (iNOS) gene expression in lipopolysaccharide (LPS) plus interferon-gamma (IFN-gamma)-stimulated RAW264.7 macrophages and investigated its mechanisms of anti-inflammatory activity.

Materials and methods: RAW264.7 macrophages were treated with 10 microg/ml LPS plus 20U/ml IFN-gamma in the presence or absence of ASE. NO production and iNOS gene expression were investigated. We further evaluated the effect of ASE on oxidative stress-sensitive transcription nuclear factor-kappa B (NF-kappaB) activation.

Results: ASE significantly suppressed NO production and iNOS gene expression in a dose-dependent manner. ASE also reduced DNA-binding activity of NF-kappaB in LPS plus IFN-gamma stimulated RAW264.7 macrophages. Further studies indicated that LPS plus IFN-gamma-induced inhibitory factor-kappa B alpha (I-kappaBalpha) degradation and p65 nuclear translocation were inhibited in RAW264.7 macrophages exposed to ASE. Moreover, ASE inhibited the LPS plus IFN-gamma mediated increase in intracellular peroxides production.

Conclusions: These results suggest ASE suppresses iNOS gene expression through the inhibition of intracellular peroxides production, which has been implicated in the activation of NF-kappaB.