Inflammation and Chronic Diseases
Inflammation is a complex series of reactions designed to prevent ongoing tissue damage and activate repair processes and defense mechanisms against infectious diseases. Prolonged inflammation, however, contributes to the pathogenesis of chronic such as Alzheimer's, diabetes, cancers, and CVD. Chronic inflammation is also believed to contribute to such eye diseases as AMD, dry eye, diabetic retinopathy and glaucoma.
Dampening inflammation may help retard the development of such diseases. Inflammatory injury may be mediated by reactive oxygen species (ROS) or their reaction products, and antioxidant therapy has been shown to prevent in vivo tissue injury during inflammation.
Role of NF-kB in the Inflammatory Response
The transcription factor nuclear factor-kB (NF-kB) controls expression of genes involved in the inflammatory response and is activated by oxidative stress and other pro-inflammatory stimuli. Activation of NF-kB results in coordinated expression of inflam-matory genes and secretion of pro-inflammatory chemokines and cytokines, which are associated with increased risk of disease and poor outcome of chronic inflammatory diseases. Thus, dampening NF-kB activation has been suggested as a strategy to prevent chronic inflammatory diseases.
Anthocyanins Dampen Inflammation
Anthocyanins are water-soluble red and blue flavonoid pigments responsible for the dark color of grapes, plums, black currants, blueberries and bilberries. The anthocyanins are effective antioxidant compounds in vitro, and have also been shown to suppress cancer, cataract, and neurodegeneration in animal models.
These data led researchers from the University of Oslo to examine whether bilberry and blackcurrant anthocyanins could inhibit NF-kB activation in vitro and in humans. The results of this study suggest that anthocyanin supplementation may have a role in pre-venting or treating chronic inflammatory diseases by inhibiting NF-kB trans-activation and deceasing plasma concentrations of pro-inflammatory chemokines, cytokines, and inflammatory mediators.
Study Design and Methods
The researchers studied whether anthocyanins inhibit LPS-induced NF-kB activation in cultured monocytes. Monocytes were pre-incubated with a combination of black currant and bilberry anthocyanins or placebo (dimethylsulfoxide). NF-kB activity was induced by LPS.
In the parallel-designed, placebo-controlled clinical study, 120 participants were randomly assigned to receive 300 mg of anthocyanins or placebo for 3 weeks. The amount of anthocyanins provided corresponded to 100 g of fresh bilberries. The subjects maintained their regular diet during the intervention period.
Blood samples from fasting at baseline and after the intervention period were collected and analyzed for cytokines [IL-1b, IL-1 receptor antagonist (IL-1Ra), IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-13, IL-17, TNFa, IFNa, IFNg, granolyte/macrophage colony-stimulating factor (GMCSF), and others were measured in plasma by a sandwich immunoassay-based protein array system.
In the cultured cells incubated with anthocyanins, NF-kB activation was suppressed by 28% compared with cells incubated with vehicle only (p = 0.003). Anthocyanins also decreased the LPS-induced p65 DNA binding, another assay for NF-kB-activation, by 18% (p =.041).
In the clinical trial, differences were observed in several NF-kB related inflammatory mediators in the anthocyanin group compared to placebo.
Decreases from baseline in the NF-kB controlled pro-inflammatory chemokines IL-8, ''regulated upon activation, normal T cell expressed and secreted,'' and IFNa (an inducer of NF-kB activation) in the anthocyanin group differed significantly from those in placebos.
Similarly, decreases from baseline in IL-4 (60%) and IL-13 (38%) in the active group differed significantly from the slight decreases seen in placebos. Both of these cytokines mediate pro-inflammatory responses and activate NF-kB.
Karlsen A , et al. Anthocyanins Inhibit Nuclear Factor-kB Activation in Monocytes and Reduce Plasma Concentrations of Pro-Inflammatory Mediators in Healthy Adults. Journal of Nutriton. 137: 1951-1954, 2007.