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Cuminum cyminum L. (cumin) is an annual plant of the Umbelliferae family native to Egypt. We previously showed that the aqueous extract of cumin seeds suppresses degranulation by downregulating the activation of antigen-induced intracellular signaling molecules in rat basophilic leukemia RBL-2H3 cells. However, the active substances in the extract have not yet been identified. Accordingly, herein, we aimed to ascertain the water-soluble substances present in cumin seeds that inhibit degranulation, which led to the identification of umbelliferose, a characteristic trisaccharide present in plants of the Umbelliferae family. Our study is the first to reveal the degranulation-suppressing activity of umbelliferose, and quantification studies suggest that cumin seed powder contains 1.6% umbelliferose. Raffinose, an isomer of umbelliferose, was also found to significantly suppress antigen-induced degranulation, but less so than umbelliferose. Both umbelliferose and raffinose contain sucrose subunits in their structures, with galactose moieties bound at different sites. These differences in structure suggest that the binding of galactose to the sucrose subunit at the α1-2 bond contributes to its strong degranulation-inhibiting properties.

Demand for novel drug screening methods which are characterized by simple, rapid and low cost is increasing now. In this study, the simple and rapid evaluation of the anti-allergic effect of natural medicines on the degranulation of a model mast cell (RBL-2H3 cells) was successfully achieved by two-dimensional surface plasmon resonance (2D-SPR) measurement. The each cell response was observed by SPR imaging upon model antigen, Albumin from bovine serum, 2, 4-Dintrophenylated (DNP-BSA) stimulation after anti-DNP IgE sensitization on RBL-2H3 cells. Here glycyrrhizic acid (GA) and isoliquiritigenin (ISL) were examined as degranulation inhibitors. After the pretreatment with 30 µmol/L GA or 50 µmol/L ISL, the reflection intensity increase at cell regions upon DNP-BSA stimulation was completely suppressed. In addition, it was shown that the suppression of reflection intensity increase at cell regions in the 2D-SPR observation upon DNP-BSA stimulation was dependent on the GA and ISL concentration in pretreatment as well as β-hexosaminidase assay. These results demonstrated that the suppression effect of GA and ISL on the degranulation of RBL-2H3 cells could be evaluated by 2D-SPR observation at cell regions in quick and simple manner. Our study further suggested that 2D-SPR observation of mast cell response might be applicable to screen anti-allergic components of natural products and useful to discuss its inhibitory effect in the intracellular signaling pathway of mast cell upon antigen stimulation.

Although Myrciaria dubia (camu-camu) has been shown to exert anti-oxidant and anti-inflammatory effects in both in vitro and in vivo studies, its use in allergic responses has not been elucidated. In the present study, the anti-allergic effect of 70% ethanol camu-camu fruit extract was tested on calcium ionophore (A23187)-induced allergies in RBL-2H3 cells. The RBL-2H3 cells were induced with 100 nM A23187 for 6 h, followed by a 1 h camu-camu fruit extract treatment. A23187 sanitization exacerbated mast cell degranulation; however, camu-camu fruit extract decreased the release of histamine and β-hexosaminidase, which are considered as key biomarkers in cell degranulation. Camu-camu fruit extract inhibited cell exocytosis by regulating the calcium/nuclear factor of activated T cell (NFAT) signaling. By downregulating the activation of mitogen-activated protein kinase (MAPK) signaling, camu-camu fruit extract hindered the activation of both histamine H1 and H4 receptors and inhibited histidine decarboxylase (HDC) expression by mediating its transcription factors KLF4/SP1 and GATA2/MITF. In A23187-induced ROS overproduction, camu-camu fruit extract activated nuclear factor erythroid-2-related factor 2 (Nrf2) to protect mast cells against A23187-induced oxidative stress. These findings indicate that camu-camu fruit extract can be developed to act as a mast cell stabilizer and an anti-histamine. This work also “opens the door” to new investigations using natural products to achieve breakthroughs in allergic disorder treatment.

Sargassum horneri (S. horneri), an edible brown alga, has been proposed as a functional food with an improvement effect on abnormal skin immune responses. The present study investigates the anti-allergic effect of an ethanol extract from S. horneri (SHE) on immunoglobulin E (IgE)/bovine serum albumin (BSA)-mediated activation in bone marrow-derived cultured-mast cells (BMCMCs) and passive cutaneous anaphylaxis (PCA) reaction in mice. SHE markedly and dose-dependently suppressed the degranulation of BMCMCs by reducing the &beta, hexosaminidase and histamine release without cytotoxicity. In addition, SHE significantly decreased the Fc&epsilon, RI expression on the surface of BMCMCs and its IgE binding. Moreover, SHE reduced the mRNA expression and the production of allergic cytokines, interleukin (IL)-1&beta, IL-4, IL-5, IL-6, IL-10, IL-13, interferon (IFN)-&gamma, and/or tumor necrosis factor (TNF)-&alpha, and a chemokine, thymus and activation-regulated chemokine (TARC), by suppressing the activation of Src-family kinases and nuclear factor (NF)-&kappa, B signaling. In further study, the application of SHE reduced the PCA reaction in an IgE/BSA-induced type I allergic mice model. Taken together, we suggest that SHE has an anti-allergic effect in type I allergic responses.

桂皮（ケイヒ）は日本薬局方に収載される生薬で，抗アレルギーや解熱鎮痛炎症薬とみなされる漢方処方に配剤される．我々はケイヒの抗アレルギー作用および抗炎症作用について調査し，活性成分の同定を行った．ケイヒを70%メタノールで抽出し（Cin70M），シリカゲルカラムクロマトグラフィー（CC）およびオクタデシルシリルCCを用いて成分を分離した．分離した画分はin vitroでの実験としてラット好塩基球性白血病細胞株（RBL-2H3）およびマウスマクロファージ細胞株（RAW264）を用い，それらが産生するサイトカインmRNAの発現率によって抗アレルギーおよび抗炎症活性を示す画分を明らかにした．また，抗アレルギー作用においては，RBL-2H3の脱顆粒率を測定するために細胞培養液中のβ - ヘキソサミニダーゼも測定した．Cin70Mとシンナムアルデヒド（CNMA）はRBL-2H3細胞における脱顆粒およびインターロイキンのmRNA発現を阻害した．CNMAは300μMで脱顆粒を抑制し，その抑制作用はポジティブコントロールとして用いたケトチフェンより僅かに強かった．同様にCin70MとCNMA はRAW264が産生した一酸化窒素（NO）および炎症性サイトカインmRNA発現を抑制した．特にNO産生についてはCNMA 100μMで10μMのデキサメタゾンと同等の抑制作用を示した．ケイヒの特徴である甘い味と芳香は明らかにした活性成分の一つであるCNMAに由来する．今回の結果から，アレルギー疾患や炎症性疾患の患者に対し，ケイヒを含む漢方薬が処方された際には甘い味と芳香が強いケイヒを選んだ方が良いことが示された．, Cinnamomi Cortex (cinnamon bark) is a major crude drug. In Japan, it is used in Kampo medicine to treatallergic and inflammatory diseases. In this study, we examined the anti-allergic and anti-inflammatoryeffects of Cinnamomi Cortex and attempted to identify its active components. Cinnamomi Cortex wasextracted with 70% methanol (Cin70M) and separated into fractions via silica gel column chromatography(CC) or octadecylsilan (ODS) CC. In order to select fractions that have anti-allergic and anti-inflammatoryactivities, we evaluated the ability of the fractions to inhibit the expression of cytokine genes in vitro byusing a rat basophilic leukemia (RBL-2H3) cell line and mouse macrophage (RAW264) cell line. Geneexpression levels were assessed in both cell lines by using semi-quantitative reverse transcriptionpolymerase chain reaction (RT-PCR), and the RBL-2H3 degranulation ratio was quantified via ???? -hexosaminidase assay. Cin70M and cinnamaldehyde (CNMA) inhibited degranulation and the mRNAexpression of interleukins in RBL-2H3 cells. CNMA inhibited degranulation at 300 ????M, and its inhibitoryeffects were slightly stronger than those of ketotifen which is a typical anti-allergic drug. In RAW264 cells,nitric oxide (NO) production and the mRNA expression of inflammatory cytokines were reduced byCin70M and CNMA. In the NO production assay, 100 ????M CNMA was found to significantly decrease NOproduction from activated RAW264 cells, and its activity was the same as that of 10 ????M dexamethasone.The taste and scent of Cinnamomi Cortex were both attributed to CNMA. The results of the presentstudy indicate that it is more beneficial for patients with allergic and/or inflammatory diseases to useCinnamomi Cortex with a strong taste and scent.

The number of individuals with allergic disease has been increasing in recent years. One suspected reason for this increase is excessive consumption of n-6 fatty acids, which are contained at high levels in vegetable oils and meats. In contrast, n-3 fatty acids are believed to have an inhibitory effect on allergic disease. Various foods including blueback fish contain high levels of n-3 fatty acids. Green nut oil（GNO）also contains approximately 50％ α-linoleic acid. Therefore, we investigated the inhibitory effect of GNO on atopic dermatitis. Four-week-old male NC/Nga TndCrlj mice were divided into a GNO-treated group and a corn oil-treated（CO）group and reared for 7 weeks. Once a week, a picryl chloride solution was applied to the backs and auricles of the mice to induce allergic dermatitis. Erythrocyte membrane and liver EPA and DHA contents were significantly higher in the GNO group compared to the CO group, suggesting that the EPA and DHA was converted from α-linoleic acid. Erythrocyte membrane and liver arachidonic acid contents were higher in the CO group. The progress of allergic disease was slower in the GNO group compared to the CO group. Blood serum IgE levels tended to be lower in the GNO group compared to the CO group, suggesting that GNO may have an anti-allergic effect.

Background: Allergic disease is a common clinical disease. Natural products provide an important source for a wide range of potential anti-allergic agents. This study was designed to evaluate the anti-allergic activities of the water-soluble polysaccharides extracted and purified from Saposhnikoviae Radix (SRPS). The composition and content of monosaccharides were determined to provide a material basis. Methods: An ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was established to determine the composition and content of SRPS. 2,4-dinitrofluorobenzene (DNFB) induced a delayed-type hypersensitivity (DTH) mouse model orally administrated SRPS for seven consecutive days. Ear swelling, organ index, and serum IgE levels were observed to evaluate the anti-allergic activities. Results: The UPLC-MS/MS analysis showed that SRPS was consisted of eight monosaccharides including galacturonic acid, mannose, glucose, galactose, rhamnose, fucose, ribose, and arabinose with a relative molar ratio of 4.42%, 7.86%, 23.69%, 12.06%, 3.10%, 0.45%, 0.71%, and 47.70%, respectively. SRPS could effectively reduce ear swelling, a thymus index, and a serum IgE levels. Conclusions: The method was simple, rapid, sensitive, and reproducible, which could be used to analyze and determine the monosaccharide composition of SRPS. The vivo experiments demonstrated that SRPS may effectively inhibit development of DNFB-induced DTH. SRPS is a novel potential resource for natural anti-allergic drugs.

The anti-allergic effect of alcohol extracts from edible seaweeds was evaluated by the degranulation of a rat basophilic leukemia cell line (RBL-2H3). Extracts prepared from the brown algae Sargassum horneri, Ecklonia cava and Ecklonia kurome, inhibited the degranulation of RBL-2H3 cells, whereas those from green algae and red algae did not. The active substance in S. horneri was purified and identified as chlorophyll c2, a major pigment in brown algae. The purified chlorophyll c2 preparation also suppressed the degranulation of RBL-2H3 cells. In contrast, chlorophyll a and b did not affect cell degranulation. Therefore, chlorophyll c2 from brown algae might be useful for the prevention or mitigation of allergic symptoms.

Quercetin is the great representative of polyphenols, flavonoids subgroup, flavonols. Its main natural sources in foods are vegetables such as onions, the most studied quercetin containing foods, and broccoli; fruits (apples, berry crops, and grapes); some herbs; tea; and wine. Quercetin is known for its antioxidant activity in radical scavenging and anti-allergic properties characterized by stimulation of immune system, antiviral activity, inhibition of histamine release, decrease in pro-inflammatory cytokines, leukotrienes creation, and suppresses interleukin IL-4 production. It can improve the Th1/Th2 balance, and restrain antigen-specific IgE antibody formation. It is also effective in the inhibition of enzymes such as lipoxygenase, eosinophil and peroxidase and the suppression of inflammatory mediators. All mentioned mechanisms of action contribute to the anti-inflammatory and immunomodulating properties of quercetin that can be effectively utilized in treatment of late-phase, and late-late-phase bronchial asthma responses, allergic rhinitis and restricted peanut-induced anaphylactic reactions. Plant extract of quercetin is the main ingredient of many potential anti-allergic drugs, supplements and enriched products, which is more competent in inhibiting of IL-8 than cromolyn (anti-allergic drug disodium cromoglycate) and suppresses IL-6 and cytosolic calcium level increase. © 2016 by the authors; licensee MDPI., internal grant agency of Tomas Bata University in Zlin [IGA/FT/2016/008, IGA ZF 2016]

The definitive version is available at www.blackwell-synergy.com, In this study, we investigated the effects of oral ingestion of Lactobacillus crispatus KT-11 strain (KT-11) on the immune response in an allergic rhinitis mouse model, ovalbumin (OVA)-sensitized BALB/c mice. Sneezing activity in mice that were administered a KT-11-supplemented diet was significantly lower than that in mice administered a KT-11-free diet (control diet) at age 11 weeks. We found that serum OVA-specific immunoglobulin E (IgE) levels and total number of interleukin (IL)-4+CD4+ spleen cells in mice that were administered a KT-11-supplemented diet were significantly lower than in mice administered a control diet. The ratio of spleen interferon-gamma+CD4+/IL-4+CD4+ cells was higher in the mice administered the KT-11-supplemented diet compared to that in mice administered the control or L. rhamnosus GG-supplemented diet. In contrast, the number of CD11b+CD80+ and Fc epsilon RI alpha+CD117+ cells was significantly lower in mice administered the KT-11-supplemented diet. These results suggested that KT-11 reduced OVA-induced allergic symptoms in BALB/c mice via the adjustment of the T helper type 1/T helper type 2 balance, and a decrease in the number of antigen-presenting cells and high affinity IgE receptor-positive mast cells., Article, ANIMAL SCIENCE JOURNAL. 81(6):699-705 (2010)

An oil of Minthostachys verticillata (Griseb.) Epling was analyzed by GC. The main constituents identified were pulegone (63.0%) and menthone (16.4%). It was found that the oil inhibited β-hexosaminidase release from basophils. Forty-two percent of the cells present in lymphocyte cultures stimulated by the oil were CD8(+) T cells and showed higher IFN-γ levels than non-stimulated cultures (p < 0.05). According to these results, the oil was considered to be a Th1 deviation inducer, inhibiting the immediate-type allergic reaction. © 2007, Taylor & Francis Group, LLC. All rights reserved. Fil: Cariddi, Laura Noelia. Universidad Nacional de Río Cuarto; Argentina Fil: Panero, Adriana. Universidad Nacional de Río Cuarto; Argentina Fil: Demo, Mirta Susana. Universidad Nacional de Río Cuarto; Argentina Fil: Sabini, Liliana Ines. Universidad Nacional de Río Cuarto; Argentina Fil: Maldonado, Ana Maria. Universidad Nacional de Río Cuarto; Argentina Fil: Grosso, Margarita. Universidad Nacional de Río Cuarto; Argentina Fil: Zygadlo, Julio Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto Multidisciplinario de Biología Vegetal. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto Multidisciplinario de Biología Vegetal; Argentina

Medicinal licorice (underground parts of Glycyrrhiza plants) is an important crude drug prescribed in many traditional Chinese formulations. Recently in China, the collection of wild Glycyrrhiza plants was restricted in 1984 because it promotes desertification. With the shortage of licorice due to this restriction, there has been a demand for the cultivation of Glycyrrhiza plants. In the former half of this review, we summarized the results of our survey of the cultivation/production state of G. uralensis in China that was performed from 1998 to 2001. In China, the cultivation of G. uralensis was initiated in the early 1990s. However, the glycyrrhizin (GL) content of the cultivated roots (mainly 3-year-old roots) we collected in our survey in China did not fulfill the standard (≥2.5%) of the Japanese Pharmacopoeia (JP XIV). Such roots cannot be used for medicine in Japan. In the latter half of this review, the results of our experiments of G. uralensis cultivation in eastern Neimenggu autonomy in China were summarized. We performed cultivation from seeds of G. uralensis, and taproots were transplanted the next year. As a result, adventitious roots collected in autumn in the 4th year after seeding conformed to the JP XIV standard for GL content. This study was the first to clarify the appropriateness of G. uralensis roots cultivated in China as a resource of medicinal licorice. The anti-allergic action of the cultivated roots and their GL bioavailability after oral administration were similar to those of existing medicinal licorice prepared from wild G. uralensis in China. These results suggest that cultivated G. uralensis roots can compensate for the insufficient licorice resources. This study not only aims at the development of licorice resources and the assessment of their standards but is also a phyto-remediation study on the global environment using cultivated plants.

Quercetin is the great representative of polyphenols, flavonoids subgroup, flavonols. Its main natural sources in foods are vegetables such as onions, the most studied quercetin containing foods, and broccoli; fruits (apples, berry crops, and grapes); some herbs; tea; and wine. Quercetin is known for its antioxidant activity in radical scavenging and anti-allergic properties characterized by stimulation of immune system, antiviral activity, inhibition of histamine release, decrease in pro-inflammatory cytokines, leukotrienes creation, and suppresses interleukin IL-4 production. It can improve the Th1/Th2 balance, and restrain antigen-specific IgE antibody formation. It is also effective in the inhibition of enzymes such as lipoxygenase, eosinophil and peroxidase and the suppression of inflammatory mediators. All mentioned mechanisms of action contribute to the anti-inflammatory and immunomodulating properties of quercetin that can be effectively utilized in treatment of late-phase, and late-late-phase bronchial asthma responses, allergic rhinitis and restricted peanut-induced anaphylactic reactions. Plant extract of quercetin is the main ingredient of many potential anti-allergic drugs, supplements and enriched products, which is more competent in inhibiting of IL-8 than cromolyn (anti-allergic drug disodium cromoglycate) and suppresses IL-6 and cytosolic calcium level increase.

The aim of the present study was to evaluate the antiallergic effect of apple condensed tannins (ACT) in patients with atopic dermatitis (AD) as a pilot study. An ACT supplement given to the patients at oral doses of 10 mg/kg per day for 8 weeks reduced the inflammation, lichenification, cracking, itching, sleep disturbance and peripheral blood eosinophil counts. Itching and sleep disturbance scores after ACT supplement even for 2 weeks were significantly decreased compared with the control group. The results suggest that ACT has an anti-allergic effect and that its use improved the symptoms of AD.