In addition, curcumin also induces apoptosis of rheumatoid arthritis-fibroblast-like synoviocytes, which are typically resistant to apoptotic signaling, by upregulating pro-apoptotic proteins, such as Bax, and downregulating the anti-apoptotic protein Bcl-2 . by regulating signaling pathways, suppressing swelling and limiting demyelination. In addition, polyphenols cause immunomodulatory effects against allergic reaction and autoimmune disease by inhibition of autoimmune T cell proliferation and downregulation of pro-inflammatory cytokines (interleukin-6 (IL-6), IL-1, interferon- (IFN-)). Herein, we summarize the immunomodulatory effects of polyphenols and the underlying mechanisms involved in the stimulation of immune reactions. and and suppress Rabbit Polyclonal to RPL39L pathogenic bacteria, such as, and [12,92]. This helps the maintenance of intestinal homeostasis and reduces swelling . Grape seed and green tea polyphenols also have potential to prevent or hold off the progression of IBD [68,94,95]. Pomegranate polyphenols also provide protecting effects against IBD by modulating the intestinal inflammatory response reducing manifestation of various pro-inflammatory cytokines, such as iNOS, COX-2, PGE2, as well as regulating the composition of the luminal microbiota . A recent study reported that diet polyphenols from mango (gallotannins and gallic acid) improved the symptoms of IBD. This study included 10 subjects who received 200C400 g/day time of mango pulp for 8 weeks. A significant reduction was observed in a factors related to neutrophil-induced swelling like IL-8, growth-regulated oncogene and granulocyte macrophage colony-stimulating element by 16.2%, 25.0% and 28.6%, respectively . Another study showed that Bronze tomatoes, which are rich in anthocyanins, flavonols, and stilbenoids, experienced a significant effect Exo1 in alleviating the symptoms of IBD in mice . Taken together, this suggests that polyphenols can help in the prevention and treatment of IBD by reducing pro-inflammatory cytokines, regulating the activity of Treg cells and advertising the growth of beneficial microbiota in the intestine. 4.2. Polyphenols and Allergies The prevalence of sensitive disorders has been increasing dramatically with competing environmental, genetic, diet and hygiene factors likely to underlie their advance [99,100]. Allergic reactions result from a hyper-reaction of the immune response against allergens such as those in the environment (dust, grass pollen) or food (milk, fish, eggs, nuts and wheat) . Because of the growing incidence, there is significant attention on interventions to assist in their management, and polyphenols have been proposed as viable solutions  (Table 2). Certain polyphenols influence allergic reactions at two essential phases: (1) allergic sensitization and (2) re-exposure to the allergen. During the sensitization phase, polyphenols such as caffeic and ferulic acid bind with allergenic proteins, forming insoluble complexes and rendering them non-reactive . Additionally, flavonoids directly affect antigen demonstration by DCs by either inhibiting cell surface manifestation of MHC-II and co-stimulatory molecules (CD80, CD86), leading to ineffective antigen demonstration, or by inhibiting cytokine production [102,103]. Polyphenols like catechins and their derivatives inhibit Th2 cytokine production [104,105] as well as T cell activation and proliferation [106,107]. Recruitment of B cells to sites of Exo1 sensitive swelling and their production of IgE have also been shown to be inhibited by polyphenols [59,108,109]. Of interest, the connection between polyphenols and proteins results in the modulation of allergic sensitization Exo1 and their direct effect on mast cells Exo1 hence inhibiting the release of allergic mediators and eventually reducing the symptoms of allergy . In addition, polyphenols such as caffeic, ferulic, and chlorogenic acids can bind irreversibly with the peanut allergens, Ara h1 and Ara h2, reducing their allergenicity . In mice, administration of polyphenol-enriched areca nut components suppressed the level of ovalbumin (OVA)-specific IgE, the manifestation of IL-4, downregulating Th2 driven immunity and enhancing the activity of myeloid-derived suppressor cells, attenuating sensitive responses . In another study, 30 woman mice treated with cranberry and blueberry polyphenol complexed peanut protein for 6 weeks, had reduced manifestation of CD63 and decreased plasma IgE levels . Evidence has also demonstrated that polyphenol-rich cranberry components interact with wheat gliadins forming insoluble complexes inside a mouse model, which decreased wheat gliadin immunogenicity and allergenicity . Furthermore, polyphenolic ellagic acid efficiently binds with allergenic proteins within the food matrix [114,115]. Punicalagin (a polyphenol derived from pomegranate), rutin and phloridzin improved the growth of beneficial bacteria species such as and which are known to have beneficial effects in food allergies [116,117]. Dental administration of a polyphenol-rich grape pores and skin extract that had been fermented with experienced an inhibitory effect on sensitive responses when compared to a non-fermented draw out . Table 2 Effect of diet polyphenols on allergic reaction. (caffeic acid, catechin, epicatechin, -sissterol, rutin, luteolin-7-glucoside, naringin, hesperidin, chlorogenic acid, and tangeretin) reduces sensitive response in mice by suppressing mast cell mediated.