Type-I allergic disorders and particularly food hypersensitivities are becoming increasingly common worldwide. This study investigated whether dietary enrichment with carotenoids inhibited oral sensitization to an antigen and the development of food allergies. The effects of a diet high in carotenoids were investigated in B10A mice that were orally sensitized to ovalbumin (OVA). The serum titers of OVA-specific immunoglobulin E (IgE), IgG1, and IgG2a were inhibited in mice fed ad libitum on a diet high in alpha- or beta-carotene compared to the control mice when orally sensitized to OVA. High alpha- and beta-carotene diets inhibited the immediate reduction in body temperature and rise in serum histamine associated with active systemic anaphylaxis in OVA-sensitized B10A mice. After re-stimulation with OVA in vitro, the production of T-helper 2-type cytokines by splenocytes from mice fed a diet high in carotenoids was lower than in control mice. Furthermore, the proportion of CD4(+) CD103(+) T cells in Peyer's patches of mice fed a carotenoid-rich diet was significantly lower than in control mice. These results suggest that an increased oral intake of carotenoids inhibits OVA-specific IgE and IgG1 production and antigen-induced anaphylactic responses by inhibiting specific T-cell activation in the mucosal immune system. A diet high in carotenoids might therefore prevent the development of food allergies.

Oenothein B is a unique macrocyclic ellagitannin dimer that has been found in various medicinal plants belonging to Onagraceae, Lythraceae, and Myrtaceae, with diverse biological activities. The immunological effects of tannins in terms of cytokine-release from macrophages and monocytes have been discussed, while the effects on other immunocompetent cells have been the subject of minimal investigation. We evaluated the immunomodulatory effects induced by tannin treatment in human dendritic cells (DCs), which play a critical role in the initial immune response, by measuring the changes in cytokine production, cell differentiation, and cell viability. Oenothein B showed significant down-regulation of the expression of cell surface molecules, CD1a and CD83, suggesting the inhibition of DC differentiation and/or maturation. The suppressive effect on DCs was associated with the induction of apoptosis without the activation of caspase-3/7, 8, and 9, and this was supported by the morphological features indicating significant nuclear condensation. Oenothein B also markedly suppressed the production of inflammatory cytokines, such as IL-1β and IL-6, in a dose-dependent manner. These data may, in part, be able to explain the traditional use of tannin-containing medicinal plants for the treatment of a variety of inflammatory diseases, including inflammatory bowel disease, celiac disease, and rheumatoid arthritis.

A novel type of encephalopathy associated with the ingestion of Sugihiratake mushroom (Pleurocybella porrigens) occurred in patients with chronic renal failure treated on hemodialysis in fall, 2004 in Japan. To clarify the mechanism of encephalopathy onset, we, for the first time, purified the cyanogen glycoside fraction (CG) from Sugihiratake mushroom using reversed phase high-performance liquid chromatography and hydrophilic interaction chromatography. Furthermore, we investigated single dose toxicity of the CG in an adenine-induced rat model of chronic renal damage (CRD). Pathological examination of kidneys indicates the development of CRD. Oral administration of the CG induces the accumulation of thiocyanate in the hemolyzed blood and brain in CRD rats, although no morphological changes were found in the brain. No further enhancement of kidney damage is observed after the oral administration of the CG in CRD rats. This is the first experimental report to suggest that acute encephalopathy, induced by Sugihiratake mushroom intake in the patients with chronic renal failure, is associated with intoxication of cyanide and thiocyanate, presumably produced metabolically produced after the ingestion of Sugihiratake mushroom.

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Apples are known to contain high concentrations of phenolic compounds such as condensed tannins. Consumption of condensed tannins has been reported to reduce the risk of many types of chronic diseases including allergies. However, their therapeutic effectiveness and potential in treating autoimmune disease remain controversial. Here, the effect of oral administration of apple condensed tannins (ACT) prepared from apples (Malus pumila cv. Fuji) on bovine type II collagen (CII)-induced arthritis in DBA1/J mice, a well-established murine model of human rheumatoid arthritis (RA), was evaluated. As compared to the control (without ACT administration) group, RA development was delayed and a significant reduction in the RA clinical score was observed in the ACT-administered group. Using cultured splenocytes isolated from CII-immunized mice, ACT-administration was shown to decrease the CII-induced increases in IL-17 expression and production in vitro. We propose that downregulation of T helper (Th) 17 cells is responsible for the ACT-induced RA suppression.