Pronthocyanidin-Rich Cranberry-FractionInduced Alteration of Periodontal Pathogen Lipopolysaccharide Functions

The cranberry (species: Vaccinium macrocarpon, family: Ericaceae) is a polyphenolicrich berry fruit native to North America and exhibits numerous beneficial properties for human health, such as inhibition of human cancer cell line proliferation and prevention of urinary tract colonization by bacterial pathogens.The proanthocyanidin rich cranberry fraction has long been speculated to possess the capacity to reduce the production of inflammatory mediators by LPSstimulated macrophages and gingival fibroblasts and to inhibit host extracellular matrix destructive enzyme production and activity.The purpose of this investigation was to examine the effect of cranberry non dialyzable material (NDM), which was shown to be rich in proanthocyanidins; this has a suppressive effect on production of inflammatory cytokines mediated by LPS which are known to play a major destructive role in periodontal disease.In addition to the cytokines, stimulation of superoxide ions by the monocytes also contributes to the severity of periodontal disease.In this study we chose to investigate the effect of NDM on LPSmediated stimulation of the cultured monocytic cells (THP-1) to secrete the two cytokines; IL-1β and TNFα, and also on superoxide release.We chose to study the effect of NDM on biological functions of isolated LPS from periodontal pathogens.LPS was isolated from P. gingivalis, T. denticola and F. nucleatum.Secretion of the two cytokines by the cultured monocytes was found to be dosedependent upon the concentration of LPS.Secretion of TNF-α varied from 110±28 to 610±42 picograms/ml (pg/ml) when stimulated cells with 1.0 and 20 ng/ml of LPS.Similarly, IL-1β secretion varied from 49±6 to 196±16 pg/ ml.The LPS of both T. denticola and F. nucleatum also exhibited similar phenomenon.In the presence of NDM (20 µg/ml), the cells secreted 80-90% less of the two cytokines when stimulated with LPS.LPS isolated from the same three oral pathogens grown in the presence of NDM (10-20 µg/ml) also failed to stimulate the monocytes compared to the LPS isolated from bacteria grown in culture media alone.Interestingly, when the THP-1 cells were first incubated with NDM, the cranberry components also caused a significant decrease in the secretion of cytokines.The results of the study strongly indicate the suppressive effect of NDM on LPS-mediated secretion of cytokines by the monocytic cells.It may be possible that the NDM may be interfering with LPS interaction with LPS binding protein and the CD-14, a known receptor on the monocytes which triggers the secretion of cytokine molecules.