Asymmetric dimethylarginine induces TNF-alpha production via ROS/NF-kappaB dependent pathway in human monocytic cells and the inhibitory effect of reinioside C

Vascul Pharmacol. 2008 Feb-Mar;48(2-3):115-21. doi: 10.1016/j.vph.2008.01.004. Epub 2008 Jan 26.

Abstract

Asymmetric dimethylarginine (ADMA), an endogenous nitric oxide synthase (NOS) inhibitor, has been implicated in vascular inflammation through induction of reactive oxygen species (ROS) and proinflammatory genes in endothelial cells. However, relatively few attentions have been paid to the effect of ADMA on monocytes, one of the important cells throughout all stages of atherosclerosis. In the present study, we found that reinioside C, the main component extracted from Polygala fallax Hemsl., dose-dependently inhibited tumor necrosis factor-alpha (TNF-alpha) production induced by ADMA in monocytes, Furthermore, reinioside C attenuated ADMA-induced generation of reactive oxygen species and activation of nuclear factor-kappaB (NF-kappaB) activity in monocytes in a dose-dependent manner, this effect was inhibited by l-arginine (NOS substrate) and PDTC (inhibitor of NF-kappaB). These data suggest that reinioside C could attenuate the increase of TNF-alpha induced by exogenous ADMA through inhibition ROS/NF-kappaB pathway in monocytes.

MeSH terms

  • Arginine / analogs & derivatives*
  • Arginine / metabolism
  • Cell Line
  • Dose-Response Relationship, Drug
  • Drugs, Chinese Herbal / isolation & purification
  • Drugs, Chinese Herbal / pharmacology*
  • Humans
  • Monocytes / drug effects*
  • Monocytes / metabolism
  • NF-kappa B / antagonists & inhibitors
  • NF-kappa B / metabolism*
  • Nitric Oxide Synthase / metabolism
  • Polygala* / chemistry
  • Pyrrolidines / pharmacology
  • Reactive Oxygen Species / metabolism*
  • Saponins / pharmacology*
  • Thiocarbamates / pharmacology
  • Tumor Necrosis Factor-alpha / metabolism*

Substances

  • Drugs, Chinese Herbal
  • NF-kappa B
  • Pyrrolidines
  • Reactive Oxygen Species
  • Saponins
  • Thiocarbamates
  • Tumor Necrosis Factor-alpha
  • reinioside C
  • pyrrolidine dithiocarbamic acid
  • N,N-dimethylarginine
  • Arginine
  • Nitric Oxide Synthase