Unusual Immuno-Modulatory Triterpene-Caffeates in the Skins of Russeted Varieties of Apples and Pears

Three triterpene-caffeates have been isolated from skins of a russeted apple cultivar Merton Russet and identified by LC-MS and NMR as betulinic acid-3-cis-caffeate, betulinic acid-3-trans-caffeate, and oleanolic acid-3-trans-caffeate. Betulinic acid-3-trans-caffeate and oleanolic acid-3-trans-caffeate were also found in russeted pear skins. These compounds have not been previously reported in apples or pears, or in any other foods. Their presence was related to suberized tissue as they were only found in russet portions of the partially russeted apple cultivar Cox's Orange Pippin and were not detected in the waxy apple cultivar Royal Gala. High concentrations of betulinic acid-3-trans-caffeate were found in the bark of both Merton Russet and Royal Gala trees. The three triterpene-caffeates showed anti-inflammatory activity in vitro, inhibiting NF-kappa B activation with IC50's of 6-9 mu M. Betulinic acid-3-trans-caffeate, the predominant compound in the apples, was immuno-modulatory at around 10 mu M in the in vitro and ex vivo bioassays, boosting production of the pro inflammatory cytokine TNF alpha in cells stimulated with bacterial lipopolysaccharides.