Malvidin-3-O-β glucoside, major grape anthocyanin, inhibits human macrophage-derived inflammatory mediators and decreases clinical scores in arthritic rats

Polyphenolic anthocyanins are major colorful compounds in red fruits, known to prevent cardiovascular and other diseases. Grape polyphenols are a mixture of various molecules and their exact contribution to above bioactivities remains to be clarified. In the present study, we first analyzed the effect of purified grape-derived compounds on human peripheral blood mononuclear cell (PBMC) survival, proliferation, as well as for their ability to inhibit the activation of human normal macrophages. Data indicated that malvidin-3-O-beta glucoside (Mal beta g), the major grape anthocyanin, is bioactive with no toxicity on human PBMC. Mal beta g decreased the transcription of genes encoding inflammatory mediators, confirmed by the inhibition of TNF alpha, IL1, IL-6 and iNOS-derived nitric oxide (NO) secretion from activated macrophages. As Mal beta g also inhibited inflammatory response of rat macrophages, we investigated the anti-inflammatory potential of Mal beta g in chronic rat adjuvant-induced arthritis (AIA). Mal beta g significantly diminished inflammatory cachexia and arthritic paw scores in AIA rats at both therapeutic and preventive levels. In vivo effects of Mal beta g correlated with down-regulation of NO generation from AIA rats' peritoneal macrophages ex vivo. These data indicate that Mal beta g, major grape anthocyanin, is a potent anti-inflammatory agent in vitro and in vivo, without detectable toxic effect. (C) 2013 Elsevier Inc. All rights reserved.