Hee Soon Shin

Oral administration of chitin and chitosan prevents peanut-induced anaphylaxis in a murine food allergy model.

Peanut allergy is IgE-mediated type-I hypersensitivity, and T helper 2 cytokines are central to those pathogenesis. We investigated the effects of the administration of chitin and chitosan on peanut-induced hypersensitivities in mouse food allergy models. Chitin and chitosan protected mice against peanut-induced anaphylaxis reactions, and the peanut-specific IgE production decreased by up to 47% with the administration of β-chitosan. The levels of IL-5, IL-13, and IL-10 were significantly suppressed in all groups (α-chitin≥β-chitin≥β-chitosan). These results suggested that the administration of chitin and chitosan from by-products of food processing are beneficial for the prevention of food allergies.

Preventive effects of skullcap (Scutellaria baicalensis) extract in a mouse model of food allergy

ETHNOPHARMACOLOGICAL RELEVANCE Food allergy, which accompanies acute symptoms such as pruritus, vomiting, diarrhea, and lethal anaphylactic shock is an increasing clinical problem. Skullcap (Scutellaria baicalensis Georgi) has been widely used as a traditional herbal medicine to treat inflammation, cancer, and allergy, but its effects in treating food allergy are not yet known. MATERIALS AND METHODS To examine the effect of skullcap on food allergy, female BALB/c mice were sensitized with 20 μg OVA and 2mg alum by intraperitoneal injection on day 0. From day 17, mice were orally challenged with OVA (50 mg) in saline every 3 days, for a total of six times. To investigate the preventive effect, skullcap (25 mg/kg) was orally administered every day from day 17 to 34. RESULTS Food allergy symptoms were evaluated by the criteria for diarrhea, anaphylactic response, and rectal temperature. Severe symptoms of food allergy were observed in the sham group (diarrhea, 3 points; anaphylactic response, 2.6 points; rectal temperature, -8.36 °C. In contrast, the skullcap treatment group had a significantly suppressed OVA-induced anaphylactic response (1.3 points) and rectal temperature (-4.76°C). Moreover, both OVA-specific IgE, Th17 cytokine (IL-17), and Th2-related cytokines (IL-4, IL-5, IL-10, and IL-13), which increased with food allergy, were significantly inhibited by skullcap treatment. CONCLUSION We demonstrate that the administration of skullcap attenuates OVA-induced food allergy symptoms through regulating systemic immune responses of Th cells. These results indicate that skullcap may be a potential candidate as a preventive agent for food allergy.

Antiallergic effect of Trigonella foenum-graecum L. extracts on allergic skin inflammation induced by trimellitic anhydride in BALB/c mice

ETHNOPHARMACOLOGICAL RELEVANCE Fenugreek (Trigonella foenum-graecum L.) has a wide variety of therapeutic properties for allergic and inflammatory diseases and is used as a traditional functional food, but its antiallergenic mechanism in these diseases is yet to be clearly elucidated. AIM In the present study, we investigated the antiallergic activity of fenugreek extract using trimellitic anhydride (TMA)-induced contact hypersensitivity (CHS) mice in vivo and ovalbumin (OVA)-immunized BALB/c mice ex vivo as represented model of T-helper (Th) 2-induced allergy. MATERIALS AND METHODS BALB/c mice were administered 250 mg/kg body weight (BW) of fenugreek extract for 7 days after sensitization and challenge treatment with 2-5% TMA. Ear thickness were noted, and the infiltration of eosinophils and mast cells was investigated by hematoxylin and eosin (H&E) and toluidine blue (TB) staining. The supernatants from homogenized ear and splenocytes were used for cytokine determination using ELISA. In addition, splenocytes from OVA-immunized BALB/c mice were treated with fenugreek extract ex vivo. The levels of cytokines present in the supernatants were determined by ELISA. The mRNA expression of T-box transcription factor 21 gene (T-bet), GATA-binding protein 3 (GATA-3), interferon (IFN)-γ, and interleukin (IL)-4 were evaluated by real-time RT-PCR. RESULTS Fenugreek extract was found to reduce ear thickness as well as the infiltration of eosinophils and mast cells. In homogenized ear, the production of IL-4, IL-5, IL-13, and IL-1β was suppressed. To determine the mechanism by which fenugreek extract inhibits allergic skin inflammation, detailed studies were conducted revealing that fenugreek extract prevented differentiation into Th2 cells in the splenocytes of OVA-induced allergic mice, resulting from suppressing the secretion of IL-4 and mRNA expression of GATA-3, an IL-4 transcription factor. In earlier phase, these extracts enhanced the secretion of IFN-γ, the mRNA expression of T-bet, an IFN-γ transcription factor, and the number of IFN-γ-producing CD4(+) T cells. CONCLUSIONS These results indicate that fenugreek extract cures Th2-induced allergic skin inflammation by enhancing Th1 differentiation. These data suggest that fenugreek extracts may prove to be an useful therapeutic agent on allergic inflammatory diseases as traditional use as well as Th2-mediated allergic response.

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.

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.

Inhibitory effect of skullcap (Scutellaria baicalensis) extract on ovalbumin permeation in vitro and in vivo

Scutellaria baicalensis Georgi (skullcap) has been widely used as a dietary ingredient. The purpose of this study was to reveal novel function of skullcap and its mechanism on allergen permeation in intestinal epithelial cells. Intestinal epithelial Caco-2 cell monolayers were used to evaluate the inhibitory effect of skullcap on ovalbumin (OVA) permeation by measuring transepithelial electrical resistance (TEER) and the quantity of permeated OVA. TEER increased and the OVA flux decreased in a dose-dependent manner through up-regulating tight junction-related proteins in cells incubated with increasing concentrations of skullcap extract. In the in vivo study, the amounts of OVA from orally ingested albumen reduced on administration of the skullcap extract. We also revealed for the first time that the active component of skullcap extract for inhibition of OVA permeation was baicalein. These findings demonstrated that skullcap extract might attenuate a food allergic response by inhibiting allergen permeation in vitro and in vivo.

Skullcap (Scutellaria baicalensis) Extract and Its Active Compound, Wogonin, Inhibit Ovalbumin-Induced Th2-Mediated Response

Skullcap (Scutellaria baicalensis) has been widely used as a dietary ingredient and traditional herbal medicine owing to its anti-inflammatory and anticancer properties. In this study, we investigated the anti-allergic effects of skullcap and its active compounds, focusing on T cell-mediated responses ex vivo and in vivo. Splenocytes from mice sensitized with ovalbumin (OVA) were isolated for analyses of cytokine production and cell viability. Mice sensitized with OVA were orally administered skullcap or wogonin for 16 days, and then immunoglobulin (Ig) and cytokine levels were measured by enzyme-linked immunosorbent assays. Treatment with skullcap significantly inhibited interleukin (IL)-4 production without reduction of cell viability. Moreover, wogonin, but not baicalin and baicalein, suppressed IL-4 and interferon-gamma production. In vivo, skullcap and wogonin downregulated OVA-induced Th2 immune responses, especially IgE and IL-5 prediction. Wogonin as an active component of skullcap may be applied as a therapeutic agent for IgE- and IL-5-mediated allergic disorders.

Inhibitory effect of unicellular green algae (Chlorella vulgaris) water extract on allergic immune response.

BACKGROUND Chlorella is used as a functional food in East Asia and has been shown to enhance immune system function. However, there has been no direct evidence of the suppressive effect of a hot water extract of Chlorella vulgaris (CVE) on histamine-mediated allergic responses. RESULTS The antihistamine activity of CVE was analysed using rat peritoneal mast cells (RPMCs) stimulated by compound 48/80. For in vivo verification, ovalbumin (OVA)-immunised BALB/c mice were treated with CVE orally. Serum immunoglobulin E (IgE) levels and splenocyte cytokine levels were determined by enzyme-linked immunosorbent assay (ELISA). CVE prevented histamine release through degranulation of mast cells by blocking the uptake of extracellular Ca²⁺ into RPMCs. Moreover, CVE administration inhibited serum IgE overproduction by OVA via induction of T helper 1 (Th1) skewing that was dependent on interferon-γ (IFN-γ) and interleukin 12 (IL-12) secretion. CONCLUSION The results of this study clearly demonstrate that CVE acts as an antiallergic dietary agent by suppressing histamine release via its enhancive effect on Th1-related responses.

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 (Ca²⁺) 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.

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.