Interleukin-1 genotype-selective inhibition of inflammatory mediators by a botanical: a nutrigenetics proof of concept.

OBJECTIVE: Although observational studies have shown that genotype may influence nutritional effects on target outcomes, there are few reported studies that stratified subjects by genotype before a nutritional intervention. This proof-of-concept trial determined whether specifically formulated botanical mixtures reduced inflammation in individuals with genetic variations that predispose to overexpression of interleukin-1beta (IL-1beta) and early heart disease. METHODS: Healthy adults with elevated C-reactive protein (CRP) were stratified into genetic groups based on being positive (IL1(Pos)) or negative (IL1(Neg)) for the at-risk IL-1 gene variations. IL1(Pos) (n = 39) and IL1(Neg) (n = 40) subjects were then randomized to the candidate botanical formulation or placebo. The botanical formulation included rose hips, a blueberry and blackberry mixture, and a grapevine extract. RESULTS: At 12 wk of dosing with the botanical formulation, IL-1beta gene expression by stimulated peripheral blood mononuclear cells was significantly lower than at baseline and significantly lower than placebo in IL1(Pos) and IL1(Neg) subjects. Mean IL-1beta gene expression treatment effect over the 12-wk period was greater in IL1(Pos) than in IL1(Neg) subjects. At 12 wk of dosing the botanical mixture produced no mean change in serum CRP levels. However, in IL1(Pos) subjects, significantly more subjects achieved a reduction in CRP with the botanical mixture than with placebo. No CRP effect was observed in the IL1(Neg) subjects. CONCLUSION: This study represents one of a few prospective clinical trials in which genetic variations were shown to differentially influence nutrient effects on outcomes.

Human gene expression as a tool to determine horticultural maturity in a bioactive plant (Echinacea purpurea L. Moench).

A phenological study was conducted to determine the impact of harvest maturity on the immune-modulating properties of Echinacea purpurea. The aerial parts of this plant were collected during seven stages of development and were assayed for a common botanical marker for this species, cichoric acid. Plants of selected development stages were also assayed for total polysaccharides and compared for their immune-modulating effects on the THP-1 monocyte/macrophage cell line by means of a gene expression study. Although the concentration of cichoric acid did not change significantly during the course of the study, stage 1 (advanced vegetative) had the highest concentration of total polysaccharides and exhibited the most potent induction activity on immune-modulating cytokines such as interferon-gamma and tumor necrosis factor-alpha. These findings suggest that the use of gene expression may be an effective tool not only to standardize botanical extracts but also to optimize harvest time.