Therapeutic Potential of Antileukotriene Drug-Camellia sinensis Extract Co-Formulation on Histamine Induced Asthma in Guinea Pigs.

BACKGROUND/OBJECTIVE: To study the therapeutic potential of Antileukotriene drug- Camellia sinensis extract co-formulation on histamine induced asthma in guinea pigs. METHODS: SRSD of Montelukast sodium was prepared by the solvent evaporation method. Lyophilized aqueous extract of Camellia sinensis leaves and SRSD mixture was filled in capsule and the capsule shell was coated to achieve initial release lag time. In vitro and pharmacokinetic study of capsules was performed and compared with commercial tablets. A further role of green tea, as an antioxidant adjunct for asthma management, has been analyzed by lung histology, mast cell count and oxidative stress assay in the serum of control and experimental animals. RESULTS: The drug release from the commercial tablet was immediate and rapid, but capsule has shown an initial 3.5 hr lag time followed by sustained action up to 8 hr. Pharmacokinetic results show that studied formulations are bioequivalent with respect to Cmax and AUC, while rest parameters showed asignificant difference. Mast cells count in lung tissue were increased (p<0.001) in the experimental group along with glycoprotein deposition in asthmatic bronchioles. Levels of SOD and GPX were decreased (p<0.05) while CAT was increased (p<0.04) in the asthma group in comparison to control. CONCLUSION: In the experimental animal model, co-formulation was effective in modulating allergic inflammation and contributing to better control of the inflammatory response. Our findings suggest that Camellia sinensis leaves extract may be used as an adjunct for future improvements in asthma treatment and prevention.

A novel concept of immunological and allergy interactions in autism spectrum disorders: Molecular, anti-inflammatory effect of osthole.

BACKGROUND: Autism spectrum disorder (ASD) is a neurodevelopmental disorder defined by Diagnosis and Statistic Manual 5 (DSM-5) as persistent social interaction and communication deficient across multiple contexts. Various immunological findings have been reported in children with ASD, and co-existing allergic problems have been recorded in children diagnosed with ASD. Osthole, the effective component of Chinese traditional medicine, is reported to have anti-inflammatory effects. This study assessed the anti-inflammatory effect of osthole on the histamine-induced inflammatory responses in PBMC cells. METHODS: Peripheral blood mononuclear cells (PBMC's) from children with: (1) ASD group with co-existing allergies/asthma (n = 29); (2) ASD group without allergy/asthma (n = 29); (3) Allergy group (n = 30) and from typically developing age-matched control subjects (n = 28) were stimulated with either histamine, FXF, osthole or mixture of this substances. mRNA COX-2 gene expression, COX-2 production and inhibitory effect of tested substances on COX-2 were assessed after stimulation. RESULTS: Children with ASD may show either an innate proinflammatory response or increased activity of COX-2 which could display more impaired behavioral profile than children with non-inflamed. This study indicated that COX-2 may be involved in pathogenesis of ASD and/or allergy, and osthole could be used to decrease the effects of COX-2 in inflammation and ASD development. High incidence of allergy in ASD patients may indicate immune dysregulation that could be of relevance to the pathophysiology, symptomatology or neuroimmunology of ASD. CONCLUSIONS: This study shows that fexofenadine (FXF - antihistamine drug) and osthole exhibit selective COX-2 enzyme inhibitory activity. The selective COX-2 activity of osthole may explain further the anti-inflammatory properties of osthole in relieving congestion in allergic rhinitis, and as distinctive effects between FXF and osthole were observed, individual antihistamines may have different modes of action via the COX enzyme system.

Attenuation of allergic responses following treatment with resveratrol in anaphylactic models and IgE-mediated mast cells.

Resveratrol exists widely in plant species and has a variety of anti-oxidant, anti-inflammatory, and immunomodulatory properties. However, there have been few reports regarding its anti-food allergic activity. In this study, we demonstrated that resveratrol (isolated from Abies georgei) could decrease the release of ß-hexosaminidase and histamine in rat basophilic leukemia-2H3 cells. Resveratrol was not only found to suppress the development of diarrhea, up-regulate the rectal temperature of ovalbumin-allergic mice, and decrease the serum level of specific immunoglobulin E, mouse mast cell protease-1 and histamine, but also found to decrease the population of dendritic cells, B cells and mast cells of ovalbumin -allergic mice in the spleen or mesenteric lymph node. Furthermore, resveratrol inhibited the release of ß-hexosaminidase and histamine in bone marrow-derived cells and alleviated mast cell-mediated passive cutaneous anaphylaxis reactions. These findings indicated that resveratrol isolated from Abies georgei might have the potential to alleviate food hypersensitivity or allergic disease.

Bamboo salt suppresses skin inflammation in mice with 2, 4-dinitrofluorobenzene-induced atopic dermatitis.

Bamboo salt (BS) is a traditional Korean food, and has been reported to have anti-cancer, anti-inflammatory, and anti-metastatic effects. However, the anti-atopic dermatitis (AD) activity of BS has not been described yet. In the present study, we examined the preventive effect of BS on AD. The effect of oral administration of BS was tested in a 2, 4-dinitrofluorobenzene (DNFB)-induced AD animal model, by histological analysis, enzyme-linked immunosorbent assay, reverse transcription-polymerase chain reaction, caspase-1 assay, and Western blotting analysis. BS administration reduced the total clinical severity and scratching frequencies, compared with the AD group. In the serum of DNFB-induced AD mice, the levels of IgE, histamine, thymic stromal lymphopoietin (TSLP), interleukin (IL)-5, and IL-13 were significantly reduced by BS treatment. BS significantly reduced the protein and mRNA expression of TSLP, IL-6, and tumor necrosis factor-α in the AD skin lesions. BS markedly reduced the infiltration of inflammatory cells. Furthermore, the activation of caspase-1 was reduced by BS in the AD skin lesions. Our results suggested that BS should be considered as a candidate treatment for allergic inflammatory diseases including AD.

Decreased viability and proliferation of CHANG conjunctival epithelial cells after contact with ultraviolet light-irradiated pollen.

CONTEXT: Contact with pollen is the major reason for the development of allergic symptoms on the ocular surface leading to a significant increase of allergic diseases worldwide. Environmental changes such as increased ultraviolet (UV) radiation and air pollution are discussed as contributory causes for this increase. OBJECTIVE: We investigated the effect of UV light on the histamine content of pollen and examined if an irradiation of pollen affects the viability and proliferation of conjunctival cells. MATERIALS AND METHODS: Alder (Alnus glutinosa) and hazel (Corylus avellana) pollen were irradiated for different time periods with sunlight, UV-A or UV-B light and the histamine content was analysed and compared with non-irradiated pollen. Conjunctival epithelial cells (CHANG cells) were exposed to irradiated and non-irradiated pollen followed by an assessment of cell viability with the colorimetric MTS test and the impedance-based measurement of cell proliferation using the xCELLigence real-time analysis system. RESULTS: UV light irradiation increased the histamine level of alder and hazel pollen in a dose-dependent manner. CHANG cells treated with irradiated pollen induced a statistically significant higher decrease of cell viability than treatment with non-irradiated pollen. DISCUSSION AND CONCLUSIONS: Our results indicate that UV light is able to alter pollen thus making them more harmful for conjunctival cells.

Anti­inflammatory effect of Amomum xanthioides in a mouse atopic dermatitis model.

Atopic dermatitis (AD) is a chronic relapsing inflammatory skin disorder. The present study investigated the effects of Amomum xanthioides extract (AXE) on AD­like skin inflammation using a Dermatophagoides farinae extract (DFE) and 2,4­dinitrochlorobenzene (DNCB)­induced mouse AD model. Hematoxylin and eosin staining results demonstrated that repeated DFE/DNCB exposure markedly increased the thickening of the dermis and epidermis, in addition to the infiltration of eosinophils and mast cells. However, oral administration of AXE reduced these histopathological alterations in a dose­dependent manner. Elevated serum histamine, total and DFE­specific immunoglobulin E (IgE), and IgG2a were also decreased by treatment with AXE. In addition, reverse transcription­quantitative polymerase chain reaction (RT­qPCR) results demonstrated that the mRNA expression of tumor necrosis factor (TNF)­α, interferon (IFN)­Î³, interleukin (IL)­4, IL­13, IL­31 and IL­17A was reduced in ear skin following AXE administration in AD mice. Fluorescence­activated cell sorting demonstrated that the population of CD4+/IL­4+, CD4+/IFN­Î³+ and CD4+/IL­17A+ cells in draining lymph nodes was also significantly decreased in AXE­treated mice compared with AD mice without AXE treatment. Furthermore, keratinocytes that were stimulated with TNF­α and IFN­Î³ exhibited increased gene expression of pro­inflammatory cytokines and chemokines, including TNF­α, IL­1ß, IL­6, IL­8, C­C motif chemokine ligand (CCL)17 and CCL22, as determined by RT­qPCR. However, upregulation of these genes was reduced by AXE pretreatment. Based on these results, we hypothesize that AXE may be useful in the treatment of allergic skin inflammation, particularly AD.

Citrus tachibana Leaves Ethanol Extract Alleviates Airway Inflammation by the Modulation of Th1/Th2 Imbalance via Inhibiting NF-κB Signaling and Histamine Secretion in a Mouse Model of Allergic Asthma.

Asthma is a chronic inflammatory disease of bronchial airway, which is characterized by chronic airway inflammation, airway edema, goblet cell hyperplasia, the aberrant production of the Th2 cytokines, and eosinophil infiltration in the lungs. In this study, the therapeutic effect and the underlying mechanism of Citrus tachibana leaves ethanol extract (CTLE) in the ovalbumin (OVA)-induced allergic asthma and compound 48/80-induced anaphylaxis were investigated. Oral administration of CTLE inhibited OVA-induced asthmatic response by reducing airway inflammation, OVA-specific IgE and IgG1 levels, and increasing OVA-specific IgG2a levels. CTLE restored Th1/Th2 balance through an increase in Th2 cytokines tumor necrosis factor-α, interleukin (IL)-4, and IL-6 and decreases in Th1 cytokines interferon-γ and IL-12. Furthermore, CTLE inhibited the total level of NF-κB and the phosphorylation of IκB-α and NF-κB by OVA. In addition, CTLE dose-dependently inhibited compound 48/80-induced anaphylaxis via blocking histamine secretion from mast cells. The anti-inflammatory mechanism of CTLE may involve the modulation of Th1/Th2 imbalance via inhibiting the NF-κB signaling and histamine secretion. Taken together, we suggest that CTLE could be used as a therapeutic agent for patients with Th2-mediated or histamine-mediated allergic asthma.

Effect of Angelica glauca essential oil on allergic airway changes induced by histamine and ovalbumin in experimental animals.

OBJECTIVE: Angelica glauca Edgew (Apiaceae) is used in traditional medicine for treatment of several diseases including bronchial asthma. The present investigation was aimed to evaluate broncho-relaxant activity of A. glauca essential oil in histamine and ovalbumin (OVA)-induced broncho constriction in experimental animals. MATERIALS AND METHODS: Airway was induced using histamine aerosol in guinea pigs (n = 24) and OVA aerosol in albino mice (n = 24). The number of inflammatory cells, namely, absolute eosinophils count in blood, total immunoglobulin E (IgE) in serum, eosinophils, and neutrophils in bronchoalveolar lavage fluid (BALF) and histopathological examination of lung tissues were investigated in A. glauca oil and dexamethasone-treated groups. A. glauca oil 200 µL/kg was given orally, and dexamethasone 2 mg/kg was given intraperitoneal. Both the treatments were repeated daily for 7 days. Results were analyzed by one-way ANOVA, and P ≤ 0.05 was considered statistically significant. RESULTS: Treatment with A. glauca essential oil significantly (P < 0.001) increased the time of preconvulsive dyspnea in histamine-induced guinea pigs. Oral treatment of A. glauca oil significantly (P < 0.001) decreased absolute blood eosinophil count (from 325 ± 3.69 to 200 ± 3.05 cells/mm3), serum level of IgE (from 6.10 ± 0.05 to 0.70 ± 0.08 IU/L), and the number of eosinophils (from 11.0% ±1.41% to 3.0% ±0.51%), neutrophils (from 13.0% ±1.12% to 5.0% ±1.39%) in BALF. Histopathological changes observed in lungs of untreated group were marked suppressed by treatment with A. glauca oil. CONCLUSION: The essential oil of A. glauca has bronchorelaxation in both histamine and OVA-induced bronchoconstriction in animals. The traditional use of A. glauca against asthma could be attributed to its bronchodilator property as observed in the present study.

Screening allergic components of Yejuhua injection using LAD2 cell membrane chromatography model online with high performance liquid chromatography-ion trap-time of flight-mass spectrum system.

Yejuhua (YJH) injection is a traditional Chinese medicine (TCM) injection and has a widely application in clinical practice. However, adverse drug reactions (ADRs) caused by YJH injection, majorly manifested as allergic reactions, have been reported. Hence, Effective and practical method for allergen screening and identification is needed. In this work, a LAD2/CMC model coupled online with HPLC-IT-TOF-MS system was developed to screen, analyze, and identify the allergenic components of YJH injection. A fraction was retained on the LAD2/CMC column, and identified as linarin (LN). Histamine release assay was performed by the multiple reaction monitoring (MRM) method of UPLC-ESI-MS/MS. Results showed that YJH injection and LN were in accord with their allergic effects by increasing histamine release. In conclusion, the LAD2/CMC-HPLC-IT-TOF-MS system developed in this study could be used to screen allergenic components in complex systems.

Reduced allergic lung inflammation by root extracts from two species of Peucedanum through inhibition of Th2 cell activation.

ETHNOPHARMACOLOGICAL EVIDENCE: Peucedani Radix (PR), the root of Peucedanum praeruptorum Dunn (PPD) or Peucedanum decursivum (Miq.) Maxim. (PDM), has long been used in Korea to eliminate sputum, relieve cough, and reduce bronchus contraction. Furthermore, these therapeutic strategies are recognized as general and effective methods in western medicine as well as traditional Korean medicine. AIM OF THE STUDY: To determine and compare the anti-inflammatory effects of PPD extracts (PPDE) and PDM extracts (PDME) on allergic lung inflammation, using in vivo OVA-induced airway inflammation in mice and in vitro primary cell culture systems. MATERIALS AND METHODS: Eight-week-old female C57BL/6 mice were placed into four groups (n=4 per group): saline control, OVA-induced allergic lung inflammation with vehicle, or PPDE (200mg/kg) or PDME (200mg/kg) treatment. PR extracts (PRE) were administered from 1 week before 1st OVA sensitization to the day before sacrifice. Mice were sacrificed 18h after last OVA intra-nasal challenge followed by histological and biochemical analyses. RESULTS: Inflammatory phenotypes were alleviated with oral administration of PRE. PRE treatment decreased mucus production in airway epithelium, inflammatory cell number, eosinophilia, type 2 cytokines, and histamine in bronchoalveolar lavage fluid (BALF). Mice with PRE administration showed diminished activated CD4 T cell (CD4+CD25+ cell) and GATA-3 level in the lung. In addition, PRE treatment reduced Th2 cell activation in vitro, using Th2 polarization system. CONCLUSION: Our findings indicate that the anti-inflammatory effects of PRE arise from reduced Th2 cell activation and validate the clinical use of PR in traditional Korean medicine.

Isoquercitrin suppresses the expression of histamine and pro-inflammatory cytokines by inhibiting the activation of MAP Kinases and NF-κB in human KU812 cells.

Mast cells and basophils are multifunctional effector cells that contain abundant secretory granules in their cytoplasm. Both cell types are involved in a variety of inflammatory and immune events, producing an array of inflammatory mediators, such as cytokines. The aim of the study was to examine whether isoquercitrin modulates allergic and inflammatory reactions in the human basophilic KU812 cells and to elucidate its influence on the phosphorylation of mitogen-activated protein kinase (MAPK) and nuclear factor (NF)-κB activation. The KU812 cells were stimulated with phorbol-12-myristate 13-acetate plus the calcium ionophore A23187 (PMACI). The inhibitory effects of isoquercitrin on the productions of histamine and pro-inflammatory cytokines in the stimulated KU812 cells were measured using cytokine-specific enzyme-linked immunosorbent (ELISA) assays. Western blotting analysis was used to assess the effects of isoquercitrin on the MAPKs and NF-κB protein levels. Our results indicated that the isoquercitrin treatment of PMACI-stimulated KU812 cells significantly reduced the production of histamine and the pro-inflammatory cytokines, such as interleukin (IL)-6, IL-8, IL-1ß, and tumor necrosis factor (TNF)-α. The treated cells exhibited decreased phosphorylation of extracellular signal-regulated kinase (ERK), revealing the role of ERK MAPK in isoquercitrin-mediated allergy inhibition. Furthermore, isoquercitrin suppressed the PMACI-mediated activation of NF-κB in the human basophil cells. In conclusion, the results from the present study provide insights into the potential therapeutic use of isoquercitrin for the treatment of inflammatory and allergic reactions.

Effects of Viola yedoensis Makino anti-itching compound on degranulation and cytokine generation in RBL-2H3 mast cells.

ETHNOPHARMACOLOGICAL RELEVANCE: The Chinese herb compound prescription Viola yedoensis Makino Anti-itching Compound (VYAC), which consists of Viola yedoensis Makino, herb, Sophora flavescens Aiton, root, and Dictamnus dasycarpus Turcz, root and rhizome, has been traditionally used to treat various skin allergic inflammatory diseases in clinic. AIM OF THE STUDY: The aim of this study is to investigate the effects of VYAC on degranulation and to determine its anti-inflammatory mechanism in RBL-2H3 mast cells. MATERIALS AND METHODS: VYAC was extracted with water-coction extraction (Shufen et al., 2012). The aqueous extracts were concentrated in vacuum under reduced pressure and lyophilized using a freeze dryer, and lyophilized powder was obtained. MTT was used to evaluate the cytotoxic of VYAC on RBL-2H3 cells. Degranulation was carried out with RBL-2H3 cell model, which was stimulated with A23187 plus PMA. ß-Hexosaminidase and histamine were measured to evaluate degranulation. The mRNA levels of inflammation cytokines (IL-1ß, TNF-α, IL-6, and iNOS) were investigated by RT-PCR to explain the anti-inflammatory mechanism of VYAC. RESULTS: VYAC did not show cytotoxic effect on RBL-2H3 cells in the range of 25-400µg/mL. A higher dose of VYAC (800µg/mL) showed significant cytotoxicity (P<0.05). VYAC could significantly inhibit ß-hexosaminidase and histamine release when treated with 100, 200, and 400µg/mL (P<0.05), but could not significantly inhibit ß-Hexosaminidase and histamine release when treated with 25 and 50µg/mL (p>0.05). The mRNA levels of inflammatory cytokines (TNF-α, IL-1ß, IL-6, and iNOS) could significantly decrease when treated with 200 and 400µg/mL (P<0.05) of VYAC, which were associated with the development of inflammation. CONCLUSIONS: Results showed that VYAC inhibited ß-hexosaminidase and histamine release, which was inhibit A23187 plus PMA stimulated RBL-2H3 cell degranulation and downregulated inflammatory cytokines (IL-1ß, TNF-α, IL-6, and iNOS) expression to block inflammatory development.

Quercetin and Its Anti-Allergic Immune Response.

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.

Antiallergic Activity of Ethanol Extracts of Arctium lappa L. Undried Roots and Its Active Compound, Oleamide, in Regulating FcεRI-Mediated and MAPK Signaling in RBL-2H3 Cells.

The antiallergic potential of Arctium lappa L. was investigated in Sprague-Dawley rats, ICR mice, and RBL-2H3 cells. Ethanol extract (90%) of A. lappa (ALE, 100 µg/mL) inhibited the degranulation rate by 52.9%, determined by the level of ß-hexosaminidase. ALE suppressed passive cutaneous anaphylaxis (PCA) in rats and attenuated anaphylaxis and histamine release in mice. To identify the active compound of ALE, we subsequently fractionated and determined the level of ß-hexosaminidase in all subfractions. Oleamide was identified as an active compound of ALE, which attenuated the secretion of histamine and the production of tumor necrosis factor (TNF)-α and interleukin-4 (IL-4) in cells treated with compound 48/80 or A23187/phorbol myristate acetate (PMA). Oleamide suppressed FcεRI-tyrosine kinase Lyn-mediated pathway, c-Jun N-terminal kinases (JNK/SAPK), and p38 mitogen-activated protein kinases (p38-MAPKs). These results showed that ALE and oleamide attenuated allergic reactions and should serve as a platform to search for compounds with antiallergic activity.

[Study on material basis of Mahuang Fuzi Xixin decoction for anti-inflammation and immune suppression based on combined method of serum pharmacochemistry and serum pharmacology].

To investigate me material basis of Mahuang Fuzi Xixin decoction (MFXD) for anti-inflammation and immune-suppression based on the combined method of serum chemical and serum pharmacological. The LC-MS/MS fingerprints of MFXD, drug-containing serum and blank serum were compared to define the components in plasma. Histamine, ß-hexosaminidase released from RBL-2H3 cell infulenced by drug-containing serum at different time points were measured by ELISA. The effect of drug-containing serum on lipopolysaccharide-induced splenocyte proliferation at different time points were determined by MTT. A correlation analysis was made on components of MFXD and pharmacological indexes based the stepwise regression method. After the intragastrical administration with MFXD, 32 components were discovered in rat serum, including 27 prototype components (10 from Mahuang, 13 from Fuzi and four from Xixin) and five unknown components. Compared with blank serum, drug-containing serum could reduce the release of histamine from RBL-2H3 induced by antigen at different time points (P < 0.05); except the 4-hour drug-containing serum, all of the remaining drug-containing serums could inhibit the RBL-2H3 mastocyte degranulation induced by antigen at different time points (P < 0.05). Drug-containing serum could significantly lipopolysaccharide-induced mouse splenocyte proliferation at 15 and 30 min (P < 0.05). A regression analysis was made on the chemical data of components absorbed into blood and pharmacological indexes, i. e. release rate of histamine, release rate of ß-hexosaminidase and inhibition rate of splenocyte. This suggested the close correlations among methyl pseudo-ephedrine, pseudoephedrine and histamine released from RBL-2H3 induced by antigen; pseudoephedrine, hypaconine, methyl pseudoephedrine and ß-hexosaminidase released from RBL-2H3 induced by antigen; as well as benzoyl hypaconine, benzoylaconine, 14-benzoyl-10-OH-mesaconine, mesaconine and lipopolysaccharide-induced mouse splenocyte proliferation. Methylpseudoephedrine, pseudoephedrine, benzoyl hypaconine, benzoylaconine and mesaconine may be part of material basis of MFXD on anti-inflammation and immune suppression.

Synthesis of ε-Viniferin Glycosides by Glucosyltransferase from Phytolacca americana and their Inhibitory Activity on Histamine Release from Rat Peritoneal Mast Cells.

Glycosylation of (+)-ε-viniferin was investigated using glucosyltransferase from Phytolacca americana (PaGT3) as a biocatalyst. (+)-ε-Viniferin was converted by PaGT3 into its 4b- and 13b-ß-D-glucosides, the inhibitory activities on histamine release from rat peritoneal mast cells of which were higher than that of (+)-ε-viniferin.

Food allergy in adolescence and adulthood.

In young children, food allergy is usually acquired via the gastrointestinal tract and directed toward egg and milk. Adolescent and adult patients, however, mainly acquire food allergy via primary sensitization to inhalant allergens on the basis of cross-reactivity between proteins in inhalant sources and in food. This type of food allergy is frequently mediated by sensitization to broadly represented allergens, or so-called panallergens. Food allergic reactions in adult patients - similar to those in children - range in severity from very mild and local symptoms, as in contact urticaria of the oral mucosa, to systemic symptoms involving distal organs, to a fatal outcome. Plant foods, such as fruits, nuts, and vegetables, are the most prevalent allergenic foods in this age group.

Allergen skin prick test should be adjusted by the histamine reactivity.

BACKGROUND: Skin prick test results are mostly reported as mean wheal diameter obtained with one concentration of allergen. Differences in technique between personnel causes variation in wheal size. The research question was whether the influence of differences in skin prick test technique among assistants and centers can be reduced by relating the allergen wheal response to that of histamine. METHODS: Two methods for estimating skin reactivity, the method of Nordic Guidelines using histamine as a reference and the method of Brighton et al. [Clin Allergy 1979;9:591-596] not using histamine as a reference, were applied to data from two biological standardization trials, using the same batch of freeze-dried timothy pollen preparation. RESULTS: The concentration defining the Nordic biological unit, defined as a concentration of allergen eliciting a wheal of the same size as that of histamine dihydrochloride 10 mg/ml, did not differ between the centers. When not using histamine as a reference, applying the method of Brighton et al., there was a 15-fold difference in the estimate of the biological activity between the trials that was eliminated by adjusting the allergen response to that of the histamine reference. CONCLUSIONS: To reduce the influence of differences in test technique among assistants and centers responses to allergen-induced skin prick tests should be compared to that of histamine.

Curine inhibits mast cell-dependent responses in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Curine is a bisbenzylisoquinoline alkaloid and the major constituent isolated from Chondrodendron platyphyllum, a plant that is used to treat inflammatory diseases in Brazilian folk medicine. This study investigates the effectiveness of curine on mast cell-dependent responses in mice. MATERIALS AND METHODS: To induce mast cell-dependent responses, Swiss mice were subcutaneously sensitized with ovalbumin (OVA-12 µg/mouse) and Al(OH)3 in a 0.9% NaCl solution. Fifteen days later, the animals were challenged with OVA through different pathways. Alternatively, the animals were injected with compound 48/80 or histamine, and several parameters, including anaphylaxis, itching, edema and inflammatory mediator production, were analyzed. Promethazine, cromoglycate, and verapamil were used as control drugs, and all of the treatments were performed 1h before the challenges. RESULTS: Curine pre-treatment significantly inhibited the scratching behavior and the paw edema induced by either compound 48/80 or OVA, and this protective effect was comparable in magnitude with those associated with treatment with either cromoglycate or verapamil. In contrast, curine was a weak inhibitor of histamine-induced paw edema, which was completely inhibited by promethazine. Curine and verapamil significantly inhibited pleural protein extravasations and prostaglandin D2 (PGD2) and cysteinyl leukotrienes (CysLTs) production following allergen-induced pleurisy. Furthermore, like verapamil, curine inhibited the anaphylactic shock caused by either compound 48/80 or an allergen. In in vitro settings, these treatments also inhibited degranulation as well as PGD2 and CysLT production through IgE-dependent activation of the mast cell lineage RBL-2H3. CONCLUSION: Curine significantly inhibited immediate allergic reactions through mechanisms more related to mast cell stabilization and activation inhibition than interference with the pro-inflammatory effects of mast cell products. These findings are in line with the hypothesis that the alkaloid curine may be beneficial for the treatment of allergic disorders.

Aceriphyllum rossii extract and its active compounds, quercetin and kaempferol inhibit IgE-mediated mast cell activation and passive cutaneous anaphylaxis.

Aceriphyllum rossii contains an abundant source of natural flavonoids with potential antioxidant, anticancer and anti-inflammatory properties. However, the effect of A. rossii extract (ARE) on immunoglobulin E(IgE)-mediated allergic responses remains unknown. In the present study, the effects of ARE and its active compounds, quercetin and kaempferol, on IgE-mediated rat basophilic leukemia mast cell activation and passive cutaneous anaphylaxis (PCA) were investigated. ARE, quercetin, and kaempferol inhibited secretion of ß-hexosaminidase and histamine, and reduced the production and mRNA expression of interleukin-4 and tumor necrosis factor-α. ARE also decreased the production of prostaglandin E2 and leukotriene B4 and expression of cyclooxygenase 2 and 5-lipoxygenase. Furthermore, ARE, quercetin, and kaempferol inhibited IgE-mediated phosphorylation of Syk, phospholipase Cγ, protein kinase C (PKC)µ, and the mitogen-activated protein kinases, extracellular signal-regulated kinase, p38, and c-Jun N-terminal kinase. ARE, quercetin, and kaempferol markedly suppressed mast cell-dependent PCA in IgE-sensitized mice. These results indicate that ARE and its active constituents, quercetin and kaempferol, may be a useful therapy for immediate-type hypersensitivity.