Glucocerebroside-Containing Milk Concentrated Powder Suppresses Oxidative Stress and Photoaging in the Skin of Hairless Mice.

This study investigated the protective effects of glucocerebroside-containing buttermilk concentrated powder (GCBM) on oxidative stress and photoaging in ultraviolet B (UVB)-irradiated hairless mice. We measured antioxidant enzyme activities, collagen synthesis-related pathways, and moisturizing-related factors in the dorsal skin of mice. We observed that dietary supplementation with GCBM increased antioxidant enzyme activity and decreased pro-inflammatory cytokine expression in the UVB-irradiated dorsal skin. Furthermore, dietary supplementation with GCBM inhibited wrinkle formation by suppressing the JNK/c-FOS/c-Jun/MMP pathway and stimulating the TGF-ßRI/Smad3/procollagen type I pathway. Dietary supplementation with GCBM also increased skin moisturization by stimulating hyaluronic acid and ceramide synthesis in the dorsal skin. Therefore, buttermilk powder supplementation helps prevent photoaging and can be used as an effective component in developing anti-photoaging products.

Silkworm dropping extract ameliorate trimellitic anhydride-induced allergic contact dermatitis by regulating Th1/Th2 immune response.

Allergic contact dermatitis (ACD) is an inflammatory skin disease caused by hapten-specific immune response. Silkworm droppings are known to exert beneficial effects during the treatment of inflammatory diseases. Here, we studied whether topical treatment and oral administration of silkworm dropping extract (SDE) ameliorate trimellitic anhydride (TMA)-induced ACD. In ACD mice model, SDE treatment significantly suppressed the increase in both ear thickness and serum IgE levels. Furthermore, IL-1ß and TNF-α levels were reduced by SDE. In allergic responses, SDE treatment significantly attenuated the production of the Th2-associated cytokine IL-4 in both ear tissue and draining lymph nodes. However, it increased the production of the Th1-mediated cytokine IL-12. Thus, these results showed that SDE attenuated TMA-induced ACD symptoms through regulation of Th1/Th2 immune response. Taken together, we suggest that SDE treatment might be a potential agent in the prevention or therapy of Th2-mediated inflammatory skin diseases such as ACD and atopic dermatitis. ABBREVIATIONS: ACD: allergic contact dermatitis; AD: atopic dermatitis; APC: antigen presenting cells; CCL: chemokine (C-C motif) ligand; CCR: C-C chemokine receptor; Dex: dexamethasone; ELISA: enzyme-linked immunosorbent assay; IFN: interferon; Ig: immunoglobulin; IL: interleukin; OVA: ovalbumin; PS: prednisolone; SDE: silkworm dropping extract; Th: T helper; TMA: trimellitic anhydride; TNF: tumor necrosis factor.

Skullcap (Scutellaria Baicalensis) Hexane Fraction Inhibits the Permeation of Ovalbumin and Regulates Th1/2 Immune Responses.

Skullcap (Scutellaria baicalensis) is well known for its anti-inflammatory and anti-allergic effects. In our previous study, we found that skullcap could inhibit allergen permeation and regulate Th1/2 immune balance. To reveal the key fractions and components of skullcap, we fractionated skullcap extract into five fractions: hexane, chloroform, ethyl acetate, butanol, and water fraction. Among these fractions, the hexane fraction significantly suppressed the production of Th2-mediated cytokines (Interleukin (IL)-4, 5, 10 and 13) and increased Th1-mediated cytokines (Interferon (IFN)-γ and IL-12). Furthermore, the hexane fraction inhibited the permeation of ovalbumin (OVA), used as an allergen, across the intestinal epithelial cell monolayer. To confirm the active compounds in the hexane fraction, fatty acids were analyzed. Linoleic acid (LA, C18:2 (>59.7%)) was identified as the most important fatty acid in the skullcap hexane fraction. LA significantly suppressed IL-4 production and increased IFN-γ secretion, as well as inhibiting OVA permeation. Thus, LA significantly diminished the permeation of allergen by enhancing intestinal barrier function and regulated allergic responses to maintain Th1/Th2 immune balance.

Baicalein induces CD4(+)Foxp3(+) T cells and enhances intestinal barrier function in a mouse model of food allergy.

The incidence of food allergy, which is triggered by allergen permeation of the gastrointestinal tract followed by a T-helper (Th) 2-mediated immune response, has been increasing annually worldwide. We examined the effects of baicalein (5,6,7-trihydroxyflavone), a flavonoid from Scutellaria baicalensis used in oriental herbal medicine, on regulatory T (Treg) cell induction and intestinal barrier function through the regulation of tight junctions in a mouse model of food allergy. An allergic response was induced by oral challenge with ovalbumin, and the incidence of allergic symptoms and T cell-related activity in the mesenteric lymph nodes were analyzed with and without the presence of baicalein. Our results demonstrated that the administration of baicalein ameliorated the symptoms of food allergy and attenuated serum IgE and effector T cells. However, Treg-related factors were up-regulated by baicalein. Furthermore, baicalein was shown to enhance intestinal barrier function through the regulation of tight junctions. We also found that baicalein treatment induced the differentiation of Treg cells via aryl hydrocarbon receptors (AhRs). Thus, the action of baicalein as an agonist of AhR can induce Treg differentiation and enhance barrier function, suggesting that baicalein might serve as an effective immune regulator derived from foods for the treatment of food allergy.

Regulatory T Cell Induced by Poria cocos Bark Exert Therapeutic Effects in Murine Models of Atopic Dermatitis and Food Allergy.

The prevalence of allergic disorders including atopic dermatitis (AD) and food allergy (FA) has increased dramatically in pediatric populations, but there is no effective drug available for their management. Therefore, trials are required for the development of safe therapeutic agents such as herbal medicines. We determined whether orally administered Poria cocos bark (PCB) extract could exert immunosuppressive effects on allergic and inflammatory symptoms of AD and FA. For both AD, which was induced using house dust mite extract, and FA, which was induced by exposure to ovalbumin, model mice were orally treated with PCB extract for 62 days and 18 days, respectively. We also investigated the inductive effect of PCB extract on the generation and maintenance of Foxp3(+)CD4(+) regulatory T cells (Tregs). The symptoms of AD and FA were ameliorated by the administration of PCB extract. Furthermore, PCB extract inhibited the Th2-related cytokines and increased the population of Foxp3(+)CD4(+) Tregs in both AD and FA models. In ex vivo experiments, PCB extract promoted the functional differentiation of Foxp3(+)CD4(+) Tregs, which is dependent on aryl hydrocarbon receptor activation. Thus, PCB extract has potential as an oral immune suppressor for the treatment of AD and FA through the generation of Tregs.

Turmeric (Curcuma longa) attenuates food allergy symptoms by regulating type 1/type 2 helper T cells (Th1/Th2) balance in a mouse model of food allergy.

ETHNOPHARMACOLOGICAL RELEVANCE: Turmeric (Curcuma longa) has traditionally been used to treat pain, fever, allergic and inflammatory diseases such as bronchitis, arthritis, and dermatitis. In particular, turmeric and its active component, curcumin, were effective in ameliorating immune disorders including allergies. However, the effects of turmeric and curcumin have not yet been tested on food allergies. MATERIALS AND METHODS: Mice were immunized with intraperitoneal ovalbumin (OVA) and alum. The mice were orally challenged with 50mg OVA, and treated with turmeric extract (100mg/kg), curcumin (3mg/kg or 30 mg/kg) for 16 days. Food allergy symptoms including decreased rectal temperature, diarrhea, and anaphylaxis were evaluated. In addition, cytokines, immunoglobulins, and mouse mast cell protease-1 (mMCP-1) were evaluated using ELISA. RESULTS: Turmeric significantly attenuated food allergy symptoms (decreased rectal temperature and anaphylactic response) induced by OVA, but curcumin showed weak improvement. Turmeric also inhibited IgE, IgG1, and mMCP-1 levels increased by OVA. Turmeric reduced type 2 helper cell (Th2)-related cytokines and enhanced a Th1-related cytokine. Turmeric ameliorated OVA-induced food allergy by maintaining Th1/Th2 balance. Furthermore, turmeric was confirmed anti-allergic effect through promoting Th1 responses on Th2-dominant immune responses in immunized mice. CONCLUSION: Turmeric significantly ameliorated food allergic symptoms in a mouse model of food allergy. The turmeric as an anti-allergic agent showed immune regulatory effects through maintaining Th1/Th2 immune balance, whereas curcumin appeared immune suppressive effects. Therefore, we suggest that administration of turmeric including various components may be useful to ameliorate Th2-mediated allergic disorders such as food allergy, atopic dermatitis, and asthma.

Enhancing Effect of Trachelogenin from Trachelospermi caulis Extract on Intestinal Barrier Function.

Trachelospermi caulis is used widely as an herbal medicine in oriental countries to attenuate fever and pain. We wished to reveal the novel function of this herb and its active component on barrier function in intestinal epithelial cells. Monolayers of intestinal epithelial cells (Caco-2) were used to evaluate the transepithelial electrical resistance (TEER) and quantity of permeated ovalbumin (OVA) as indices of barrier function. T. caulis increased TEER values on cell monolayers and decreased OVA permeation across cell monolayers. To ascertain the active component of T. caulis, the extract was isolated to five fractions, and the effect of each of these fractions on intestinal barrier function examined. Chloroform and ethyl acetate fractions showed increased TEER values and decreased OVA flux. Chloroform and ethyl acetate fractions contained mainly trachelogenin and its glycoside, tracheloside. Trachelogenin increased TEER values and decreased OVA flux by enhancing the tight-junction protein occludin (but not tracheloside) in Caco-2 monolayers. These findings demonstrated that trachelogenin, an active component of T. caulis, might help to attenuate food allergy or inflammatory bowel disease through inhibition of allergen permeation or enhancement of the intestinal barrier.

Cheonggukjang ethanol extracts inhibit a murine allergic asthma via suppression of mast cell-dependent anaphylactic reactions.

Cheonggukjang (CGJ), a traditional Korean fermented soybean food, exerts immunomodulatory effects. Asthma is the most common chronic allergic disease to be associated with immune response to environmental allergens. In the pathogenesis of asthma, histamine is one of the important inflammatory mediators released from granules of mast cells. In this study, we evaluated the therapeutic effect of CGJ on a mouse model of ovalbumin (OVA)-induced asthma via the suppression of histamine release. C57BL/6 mice were sensitized by intraperitoneal injection of OVA or a phosphate-buffered saline (PBS) control and then challenged with OVA inhalation. Mice were treated intraperitoneally with either 70% ethanol-extracted CGJ (CGJE) (100 mg/kg/day) or equivalent PBS. Asthma-related inflammation was assessed by bronchoalveolar lavage fluid cell counts and histopathological and immunohistochemical analysis of lung tissues. To elucidate the mechanisms of asthma inhibition by CGJE treatment, we also examined degranulation and histamine release of compound 48/80-induced rat peritoneal mast cells (RPMCs). Treatment with CGJE downregulated the number of eosinophils and monocytes in the lungs of mice challenged with OVA and suppressed histopathological changes, such as eosinophil infiltration, mucus accumulation, goblet cell hyperplasia, and collagen fiber deposits. Moreover, CGJE alleviated compound 48/80-induced mast cell degranulation and histamine release from RPMCs through inhibition of calcium (Ca²âº) uptake as well as ear swelling by infiltration of inflammatory cells. These findings demonstrated that CGJE can be used as an antiasthmatic dietary supplements candidate for histamine-mediated asthma.