Additive and Synergistic Modulation of LPS-induced NF-kappa B Activity by Dietary Plant Extracts

Abstract

Epidemiological studies have shown that a high intake of fruits and vegetables is associated with a reduced risk of chronic diseases. The mechanisms behind these beneficial effects are not fully understood, but it is widely believed that the numerous phytochemicals found in plants and interactions between them plays an important role. In the present work 8 different dietary plant extracts are selected on basis of their high phytochemical content and their ability to inhibit the transcription factor NF-kappa B. NF-kappa B is essential in normal immune responses and cell survival, but is also up-regulated in conditions like chronic inflammation and certain cancers. The purpose of this work was to elucidate whether combinations of the extracts have an additive or synergistic effect on NF-kappa B activation under an acute inflammatory condition in a monocytic cell line. In addition we studied the effect of a combination extract on NF-kappa B activation in vivo in transgenic mice. Out of 22 combinations tested in vitro, 10 showed a synergistic effect on LPS-induced NF-kappa B activity. The combination of oregano and coffee showed the strongest synergistic effect with 46 % lower NF-kappa B activity than the sum of effects of the two individual extracts. Coffee, oregano and thyme were each present in 4 of the 10 combinations that showed synergistic effects. In addition, 10 of the 22 combinations showed an additive effect or a trend towards synergy. The in vivo experiment showed that a combination of thyme, clove, oregano, coffee and walnut gave a trend towards inhibition of LPS-induced NF-kappa B activity in whole mice. The combination-extract significantly inhibited LPS-induced NF-kappa B activity in the intestine and showed a trend towards lower NF-kappa B activation in the liver. This is the first study to show synergistic effect of dietary components on NF-kappa B activation. Based on these results further work with food synergy is warranted.