Malvidin-3-O-ß 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-ß glucoside (Malßg), the major grape anthocyanin, is bioactive with no toxicity on human PBMC. Malßg decreased the transcription of genes encoding inflammatory mediators, confirmed by the inhibition of TNFα, IL1, IL-6 and iNOS-derived nitric oxide (NO) secretion from activated macrophages. As Malßg also inhibited inflammatory response of rat macrophages, we investigated the anti-inflammatory potential of Malßg in chronic rat adjuvant-induced arthritis (AIA). Malßg significantly diminished inflammatory cachexia and arthritic paw scores in AIA rats at both therapeutic and preventive levels. In vivo effects of Malßg correlated with down-regulation of NO generation from AIA rats' peritoneal macrophages ex vivo. These data indicate that Malßg, major grape anthocyanin, is a potent anti-inflammatory agent in vitro and in vivo, without detectable toxic effect.

Production of highly 13C-labeled polyphenols in Vitis vinifera cell bioreactor cultures.

The use of Vitis vinifera cells grown in a 2 l-stirred tank bioreactor for producing isotopically 13C-labeled phenolic substances is presented. Several culture parameters were optimized to achieve characteristics of growth and polyphenol metabolism similar to that recorded in shake flasks. Administration of [1-13C]L-phenylalanine (3 mM) to grape cell suspension cultures led to the production of 13C-labeled stilbenes (trans- and cis-piceids), catechins (catechin and epicatechin) and anthocyanins (delphinidin-, cyanidin-, petunidin-, peonidin- and malvidin-3-O-beta-glucosides). Incorporation of [1-13C]L-phenylalanine into polyphenols was measured by means of 13C satellites in the proton NMR spectrum and EA-IRMS. The enrichment of labeling obtained for all the compounds (between 40 and 65%) is sufficient to investigate their absorption and metabolism in humans.