In-vitro and in-vivo anti-allergic effects of magnolol on allergic rhinitis via inhibition of ORAI1 and ANO1 channels.

ETHNOPHARMACOLOGICAL RELEVANCE: Flos Magnoliae (the dried flower buds of Magnolia biondii Pamp, FM) is a known herbal traditional medicine used for the symptomatic relief of nasal congestion and rhinorrhea caused by rhinitis and sinusitis. Magnolol, a neolignan from the magnolia family, is a secondary metabolite known to have anti-allergic and anti-inflammatory effects. However, the underlying mechanisms and therapeutic effect of magnolol in the treatment of allergic rhinitis (AR) remain elusive. AIMS OF THE STUDY: Anoctamin 1 (ANO1), a calcium-activated anion channel, mediates mucus and electrolyte secretion in nasal airway epithelial cells, whereas calcium release-activated calcium channel protein 1 (ORAI1) participates in the activation of T-lymphocytes and mast cells. The aim of our study is to understand the mechanisms of action of magnolol against AR, i.e., whether it acts through the modulation of ANO1 and ORAI1 channels that are expressed in nasal epithelial cells and T-lymphocytes, respectively. MATERIALS AND METHODS: Whole-cell patch clamp was used to record the activity of ORAI1 and ANO1 ion channels in ORAI1 or ANO1 overexpressed HEK293T cells, while the Ussing chamber apparatus was used to measure electrolyte transport via the epithelium, in Calu-3 cells cultured in an air-liquid interface. Additionally, calcium imaging of Jurkat T-lymphocytes was used to assess changes in the intracellular calcium concentration. Magnolol toxicity was assessed using the CCK-8 assay, and its effect on T-lymphocyte proliferation was measured by labeling human primary T-lymphocytes with carboxyfluorescein succinimidyl ester. Finally, OVA-induced Balb/c mice were employed to evaluate the effect of magnolol on nasal symptoms, as well as cytokine and eosinophil infiltration in AR. RESULTS: Magnolol inhibits ORAI1 and ANO1 channels in a concentration-dependent manner. Magnolol (30 µM) inhibits anti-CD3 induced cellular proliferation and production of IL-2 via ORAI1 channels in T-lymphocytes. Further, ATP-induced electrolyte transport mediated by ANO1 channels is significantly inhibited by magnolol in IL-4 sensitized Calu-3 cells. Notably, 300 µM magnolol significantly attenuates cytokine and eosinophil infiltration, thus alleviating AR symptoms in mice OVA-induced AR. CONCLUSION: Magnolol may be a promising therapeutic agent for the treatment and prevention of AR.

Anti-allergic effects of Asarum heterotropoides on an ovalbumin-induced allergic rhinitis murine model.

Allergic rhinitis (AR) is a common chronic respiratory disease. Asarum heterotropoides (AH) is predicted to be a treatment for allergic diseases, but its therapeutic effect is unclear. We aimed to determine the anti-allergic effects of AH in mice with ovalbumin (OVA)-induced AR. OVA-induced AR mouse model was constructed, and AH was orally administered for a week; next, nasal clinical symptoms were evaluated. The levels of serum histamine, OVA-specific IgE, and IL-13 were measured by ELISA. Inflammatory cells, including leukocytes, neutrophils, eosinophils, and macrophages were counted in the nasal lavage fluid (NALF). Histopathological examinations of the nasal tissues were performed using H&E, Giemsa, and PAS staining. The production of periostin and eotaxin-3 from AH-treated human nasal epithelial cells (HNEpCs) in vitro, was measured using ELISA. Oral administration of AH alleviated allergic symptoms in mice with AR; significantly decreased levels of allergic mediators, such as serum histamine and OVA-specific IgE. The decrease in allergic symptoms positively correlated with the decrease in serum allergic mediators. The NALF of AH-treated AR mice demonstrated lower number of eosinophils. AH demonstrated a capacity to reduce the infiltration of mast cells, eosinophils, and goblet cells, thereby resulting in thinner nasal tissues. Moreover, treatment of HNEpCs with AH demonstrated suppressed production of periostin and eotaxin-3. AH exerts a therapeutic effect in modulating AR through multi-target and multi-function influence on regulating B cells, mast cells, eosinophils, goblet cells, and epithelial cells.

Anti-allergic Inflammatory Components from the Leaves of Piper crocatum Ruiz & Pav.

Piper crocatum Ruiz & Pav. (P. crocatum), a traditional medicinal plant, has been shown to possess various pharmacological activities, including anticancer activity, antioxidant activity, antibacterial activity, anti-hyperglycemic activity, anti-allergic inflammatory activity and others. To identify the potential anti-allergic inflammatory effective constituents of P. crocatum, 13 single compounds were isolated from the methanol extract of P. crocatum leaves, and their structures were identified by contrasting their NMR spectroscopic data and previously published papers. First, the anti-allergic inflammatory activities of these single compounds were examined by accessing immune function related biomarkers such as nitric oxide (NO) and ß-hexosaminidase. We found that the methanol extract and catechaldehyde (compound 1) potently suppressed NO production. Additionally, Western blot analysis showed that P. crocatum methanol extract and compound 1 suppressed the production of NO by reducing inducible nitric oxide synthase (iNOS) expression in lipopolysaccharide (LPS)-induced RAW264.7 macrophages. Consistent with these observations, P. crocatum methanol extract and compound 1 remarkably decreased ß-hexosaminidase release from RBL-2H3 cells stimulated with 2,4-dinitrophenylated bovine serum albumin (DNP-BSA)-specific immunoglobulin E (IgE) antibodies. Furthermore, 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay indicated that P. crocatum methanol extract and compound 1 exhibited no cytotoxicity to RAW264.7 and RBL-2H3 cells. Based on these findings, compound 1 is suggested as an active anti-allergic inflammatory component of P. crocatum.

Immunostimulatory and anti-allergic potential of novel heterotrimeric lectin from seeds of Zizyphus mauritiana Lam.

Zizyphus mauritiana Lam. seeds (ZMS) have been used medicinally as sedative or hypnotic drugs in most of Asian countries. ZMS has significant benefits to the human health. Therefore, we have evaluated immunomodulatory effect of lectin extracted from these ZMSL in both in vitro and in vivo study. Anaphylaxis is a severe life-threatening allergic reaction and Arthus reaction is deposition of immune complex and complement system activation, so we hypothesized that if ZMSL can protect these severe allergic diseases. We have studied the effect of ZMSL on macrophages and Wistar albino rats and confirmed its protective effect against anaphylaxis and Arthus reaction. Results of this study suggest ZMSL have immunostimulatory and antiallergic activity.

Sophoricoside from Sophora japonica ameliorates allergic asthma by preventing mast cell activation and CD4+ T cell differentiation in ovalbumin-induced mice.

Asthma is a chronic inflammatory lung disorder with continuously increasing prevalence worldwide. Novel strategies are needed to prevent or improve asthma. The aim of this study was to investigate the effects of sophoricoside from Sophora japonica on allergic asthma. The mature seeds of S. japonica contain a large amount of sophoricoside. Sophoricoside reduced allergic and asthmatic symptoms by suppressing airway inflammation and antibody-antigen reaction in mouse models. In particular, sophoricoside suppressed immune cell recruitment into the airway lumens of the lungs and production of pro-inflammatory cytokines in the bronchoalveolar lavage fluid (BALF) of ovalbumin (OVA)-induced mice. It also decreased the amounts of histamine and arachidonic acid metabolites released in OVA-induced mice and antibody-antigen stimulated mast cells. In addition, sophoricoside decreased differentiation of naïve CD4+ T cells into T helper type 1 (Th1), Th2, and Th17 cells. Overall, we demonstrated that sophoricoside improved allergic asthma by suppressing mast cell activation and CD4+ T cell differentiation.

Inhibitory Effects of Green Asparagus Extract, Especially Phospholipids, on Allergic Responses in Vitro and in Vivo.

Asparagus (Asparagus officinalis L.) is one of the widely consumed vegetables. To investigate the mechanism underlying the anti-allergic responses of asparagus, we extracted different fractions from asparagus and measured their inhibitory effects on ß-hexosaminidase release in RBL-2H3 cells in vitro and an atopic dermatitis NC/Nga mouse model in vivo. The lipid fractions from asparagus were extracted with 50% ethanol, separated using chloroform by liquid-liquid phase separation, and fractionated by solid-phase extraction. Among them, acetone fraction (rich in glycolipid) and MeOH fraction (rich in phospholipid) markedly inhibited ß-hexosaminidase release from RBL-2H3 cells. In NC/Nga mice treated with picryl chloride, atopic dermatitis was alleviated following exposure to the 50% EtOH extract, acetone fraction, and methanol fraction. The inhibitory effects of asparagus fractions in vivo were supported by the significant decrease in serum immunoglobulin E (IgE) levels. The phospholipid fractions showed significantly better inhibitory effects, and phosphatidic acid from this fraction showed the best inhibitory effect on ß-hexosaminidase release. In mice challenged with ovalbumin (OVA), oral administration of asparagus extract and its fractions decreased the OVA-specific IgE level and total IgE, indicating that these effects may be partly mediated through the downregulation of antigen-specific IgE production. Taken together, the present study shows for the first time that asparagus extract and its lipid fractions could potentially mitigate allergic reactions by decreasing degranulation in granulocytes. Our study provides useful information to develop nutraceuticals and functional foods fortified with asparagus.

Identification of pyrogallol from Awa-tea as an anti-allergic compound that suppresses nasal symptoms and IL-9 gene expression.

As the expression level of allergic disease sensitive genes are correlated with the severity of allergic symptoms, suppression of these gene expressions could be promising therapeutics. We demonstrated that protein kinase Cδ / heat shock protein 90-mediated H1R gene expression signaling and nuclear factor of activated T-cells (NFAT)-mediated IL-9 gene expression signaling are responsible for the pathogenesis of pollinosis. Treatment with Awa-tea combined with wild grape hot water extract suppressed these signaling and alleviated nasal symptoms in toluene-2,4-diisocyanate (TDI)-sensitized rats. However, the underlying mechanism of its anti-allergic activity is not elucidated yet. Here, we sought to identify an anti-allergic compound from Awa-tea and pyrogallol was identified as an active compound. Pyrogallol strongly suppressed ionomycin-induced up-regulation of IL-9 gene expression in RBL-2H3 cells. Treatment with pyrogallol in combination with epinastine alleviated nasal symptoms and suppressed up-regulation of IL-9 gene expression in TDI-sensitized rats. Pyrogallol itself did not inhibit calcineurin phosphatase activity. However, pyrogallol suppressed ionomycin-induced dephosphorylation and nuclear translocation of NFAT. These data suggest pyrogallol is an anti-allergic compound in Awa-tea and it suppressed NFAT-mediated IL-9 gene expression through the inhibition of dephosphorylation of NFAT. This might be the underlying mechanism of the therapeutic effects of combined therapy of pyrogallol with antihistamine. J. Med. Invest. 67 : 289-297, August, 2020.

Protective effect of Asarum sieboldii essential oil on ovalbumin induced allergic rhinitis in rat.

BACKGROUND: The study was aimed to investigate the protective effect of Asarum sieboldii Miq. essential oil (AEO) on ovalbumin (OVA)-induced allergic rhinitis (AR) in rats. METHODS AND RESULTS: Sixty Sprague-Dawley male rats were randomly divided into six groups (n=10): control, model, cetirizine (Cet, 4.65 g/kg), and AEO (0.5, 1.5, 3 g/kg) groups. All animals except the control group received repeated intranasal instillation with 20 µl of 20% OVA in Al(OH)3 saline solvent for 15 days. The control group was intranasally instilled with 5 mg/ml of Al(OH)3 instead of the same procedure. In the 15 days, Cet and AEO were orally administrated for 28 days. At the end of the drug administration, 20 µl of 5% OVA was given to animals to stimulate allergic reaction, then the rat behavioral detection, assessment of the patho-morphological changes in nasal mucosa, and the serum biomarkers were determined. The result showed that AEO could significantly reduce the amount of nasal secretions, sneezing, and the degree of nasal scratching in AR rats with EC50 = 1.5 and 2.8 g/kg, respectively. The degree of nasal mucosal inflammation in AEO group improved, the levels of immunoglobulin E (IgE), histamine, IL-4, IL-5, IL-17 were decreased, and the level of IFN-γ was increased obviously with EC50 = 2 g/kg. CONCLUSION: The study suggested that the possible mechanism might be related with the inhibition of histamine release and regulation of the cytokine levels, which plays an important role in the treatment of AR.

Inhibitory Effects of Eriodictyol-7-O-ß-d-glucuronide and 5,7-Dihydroxy-4-chromene Isolated from Chrysanthemum zawadskii var. latilobum in FcεRI-Mediated Human Basophilic KU812F Cell Activation.

Chrysanthemum zawadskii var. latilobum (CZL) has been used in Eastern medicine for the treatment of various diseases, such as pneumonia, bronchitis, cough, the common cold, pharyngitis, bladder-related disorders, gastroenteric disorders, and hypertension. In the present study, we isolated two strong antiallergic compounds from CZL, namely, eriodictyol-7-O-ß-d-glucuronide (EDG) and 5,7-dihydroxy-4-chromene (DC), and investigated their antiallergic effects in FcεRI-mediated human basophilic KU812F cells. EDG and DC downregulated the protein and messenger RNA (mRNA) expression of FcεRI on the cell surface. Moreover, Western blotting analysis showed that EDG and DC inhibited the expression of protein tyrosine kinases such as Syk and Lyn, and extracellular-regulated kinases (ERK) 1/2. These results suggested that EDG and DC, antiallergic constituents of CZL, are potential therapeutic candidates for protection against and for the treatment of allergic disorders.

Sulforaphane mitigates mast cell-mediated allergic inflammatory reactions in in silico simulation and in vitro models.

Objectives: Sulforaphane, a major ingredient isolated from Brassica oleracea var. italica (broccoli), is known to exhibit anti-inflammatory, anti-cancer, and anti-diabetic effects. In this study, we employed an in vitro model of phorbol 12-myristate 13-acetate and a23187 (PMACI)-stimulated human mast cells (HMC-1 cells) to investigate the anti-allergic inflammatory effects and mechanisms of sulforaphane and Brassica oleracea var. italica extracts.Methods: Cytokine levels were measured by ELISA and quantitative real-time-PCR methods. Caspase-1 activity was determined by caspase-1 assay. Binding mode of sulforaphane within caspase-1 was determined by molecular docking simulation. Protein expression was determined by Western blotting.Results: Water extract of Brassica oleracea var. italica (WE) significantly reduced thymic stromal lymphopoietin (TSLP) secretion and caspase-1 activity on activated HMC-1 cells. In the molecular docking simulation and in vitro caspase-1 assays, sulforaphane regulated caspase-1 activity by docking with the identical binding site of caspase-1. Sulforaphane significantly inhibited the levels of inflammatory mediators including TSLP, tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6, and IL-8 in a dose-dependent manner. Immunoblotting experiments revealed that sulforaphane and WE reduced translocation of NF-κBp65 into the nucleus and phosphorylation of IκBα in the cytosol. Furthermore, phosphorylation of mitogen-activated protein kinases (MAPK) was down-regulated by treatment with sulforaphane or WE.Conclusion: Our findings suggest that sulforaphane and WE have anti-allergic inflammatory effects by intercepting caspase-1/NF-κB/MAPKs signaling pathways.

Agaricus blazei-Based Mushroom Extract Supplementation to Birch Allergic Blood Donors: A Randomized Clinical Trial.

Since Agaricus blazei Murill (AbM) extract reduced specific IgE and ameliorated a skewed Th1/Th2 balance in a mouse allergy model, it was tested in blood donors with self-reported, IgE-positive, birch pollen allergy and/or asthma. Sixty recruited donors were randomized in a placebo-controlled, double-blinded study with pre-seasonal, 7-week, oral supplementation with the AbM-based extract AndosanTM. Before and after the pollen season, questionnaires were answered for allergic rhino-conjunctivitis, asthma, and medication; serum IgE was measured, and Bet v 1-induced basophil activation was determined by CD63 expression. The reported general allergy and asthma symptoms and medication were significantly reduced in the AbM compared to the placebo group during pollen season. During the season, there was significant reduction in specific IgE anti-Bet v 1 and anti-t3 (birch pollen extract) levels in the AbM compared with the placebo group. While the maximal allergen concentrations needed for eliciting basophil activation before the season, changed significantly in the placebo group to lower concentrations (i.e., enhanced sensitization) after the season, these concentrations remained similar in the AndosanTM AbM extract group. Hence, the prophylactic effect of oral supplementation before the season with the AbM-based AndosanTM extract on aeroallergen-induced allergy was associated with reduced specific IgE levels during the season and basophils becoming less sensitive to allergen activation.

Effects of a Novel Barley-Based Formulation on Allergic Rhinitis: A Randomized Controlled Trial.

OBJECTIVE: Current treatment options for Allergic Rhinitis (AR) may have their own limitations and side effects. This study aimed to investigate the effects of Ma-al-Shaeer (MS), a novel natural formulation based on Hordeum vulgare, in the treatment of AR compared with Fexofenadine (FX). METHODS: A total of 77 patients with AR were divided into two groups: MS group (n=38) and FX group (n=39). The first group received 15 g of dried MS powder, and the second group received 60 mg of FX twice daily for 14 days. At baseline (week zero) and after the 14-day treatment period (week two), both groups were evaluated for sneezing, rhinorrhea, nasal congestion, nasal itching, post nasal drip, eye, throat, or ear symptoms, headache, cough, mental function, quality of life scores, blood eosinophil count and total IgE levels. Rhinitis control assessment tests were conducted at week zero and again at one week after cessation of treatment (week three) in both groups. RESULTS: All symptoms of AR except cough were significantly reduced in both groups; for nasal congestion, post nasal drip, and headache, the MS treatment was found to be superior. Rhinitis control was significantly increased after treatment in both groups (p value < 0.001). Both drugs significantly reduced total IgE levels. There was no significant change in eosinophil count in either group. CONCLUSION: MS formulation based on H. vulgare may be an effective treatment for AR. Further studies are needed to confirm the effect of MS as an alternative treatment in AR.

Biosynthesis of gold nanoparticles using Caffeoylxanthiazonoside, chemical isolated from Xanthium strumarium L. fruit and their Anti-allergic rhinitis effect- a traditional Chinese medicine.

This study significantly aims to analyze the effect of CFX coated gold nanoparticles on the allergic rhinitis in mouse model. Female BALB/C mice were intraperitoneally injected with ovalbumin and aluminum hydroxide in order to sensitize on 0th, 7th, 14th, and 21st day. Nano­gold was also nasally inoculated earlier to the intranasal administration of OVA. The acuteness of allergic rhinitis was evaluated based on the nasal indications, interleukin IL-4, and interferon (INF)-γ levels present in the NLF of mice. Also, Hematoxylin-eosin as well as Schiff-periodic acid stain assays were carried out to briefly investigate the histological modifications in the sensitized mice. Nano­gold reduced the incidence of nasal symptoms as well as minimized the IL-4 production, no impact was showed over the levels of INF-γ. Further, the extent of inflammatory cell intrusion was also influenced by the CFX/AuNPs. These experimental findings manifested that AuNPs may considerably inhibit the allergic inflammation in mice models and may be expected to serve as anti-allergic rhinitis agents.

Inhibitor for FcεRI expression on mast cell from Verbasucum thapsus L.

We found out 2',3'-dihydroxypuberulin from South American medicinal plant, V. thapsus L., as a candidate of an anti-allergic lead which inhibits the expression of high-affinity receptor of IgE (FcεRI) on the surface of mast cells. Furthermore, the analysis of structure-activity relationship by using synthesized 2',3'-dihydroxypuberulin analogs revealed that both hydroxy groups in the side chain and both of methyl moieties on phenolic hydroxy groups were crucial for potent activity, but absolute configuration of C-3' position wasn't. The active principle, 2',3'-dihydroxypuberulin, was disclosed to down-regulate the mRNA level of ß-chain of FcεRI, different from previous reported active natural product reducing γ-chain level.

Anti-allergic inflammatory components from Sanguisorba officinalis L.

Sanguisorba officinalis L. was well known as a traditional herbal medicine to treat inflammation and allergic skin diseases. The aim of this research was to indentify compounds with anti-allergic inflammatory property. Twenty-five compounds (1-25) were isolated from S. officinalis including two new compounds (1 and 8), and their chemical structures were identified by NMR and ESIMS analysis. Consequently, the anti-allergic inflammatory activities of these isolates were investigated by inhibiting ß-hexosaminidase and IL-4 production in PMA/A23187-stimulated RBL-2H3 cells. Compounds 6, 8, 13, 17-18 and 25 significantly inhibited ß-hexosaminidase release and IL-4 production. Additionally, compounds 8, 17 and 25 effectively suppressed the activation of NF-κB and NF-κB p65 translocation into the nucleus. Anti-inflammatory effects of isolated compounds were evaluated in LPS-stimulated RAW264.7 macrophages, and they showed dramatic inhibition on LPS-induced overproduction of nitric oxide (NO) and TNF-α. Consistently, the protein levels of iNOS and COX-2 were remarkably decreased by the single compounds 8, 13 and 25. These results showed that compounds 8, 13 and 25 from S. officinalis may have a therapeutic potential for allergic inflammatory diseases.

Anti-allergy activities of Kuji amber extract and kujigamberol.

Amber is fossilized tree resin and several biologically active compounds were isolated from ambers using the growth-restoring activity of the mutant yeast [Saccharomyces cerevisiae (zds1∆ erg3∆ pdr1∆ pdr3∆)] involving Ca2+-signal transduction. The aim of this study is to investigate the anti-allergic effect of both the methanol extract of Kuji amber (MEKA) and its main biologically active constituent, kujigamberol (15,20-dinor-5,7,9-labdatrien-18-ol) having activity against the mutant yeast. Both MEKA and kujigamberol inhibited the degranulation of RBL-2H3 cells by stimulation of thapsigargin (Tg) (IC50 = 15.0 µg/ml and 29.1 µM) and A23187 (IC50 = 19.6 µg/ml and 24.9 µM) without cytotoxicity, but not by stimulation of IgE + DNP-BSA (Ag) (IC50 > 50.0 µg/ml and 50.0 µM). However, both inhibited Ca2+-influx in RBL-2H3 cells by all three stimulations in a dose dependent manner. Leukotriene C4 production in RBL-2H3 cells stimulated by A23187 was also inhibited by both through the inhibition of ERK1/2 phosphorylation. In an ovalbumin-induced rhinitis model of guinea pigs, nasal administration of MEKA and kujigamberol inhibited nasal blockade in a dose-dependent manner and the effect was about 5 times potent than that of a steroid clinical drug, mometasone furoate. The growth-restoring activity of MEKA and kujigamberol against the mutant yeast is involved in the anti-allergic activities against cells and animals, and both are expected to be candidates for the development of new anti-allergy agents.

Antiallergic and antihistaminic actions of Ceasalpinia bonducella seeds: Possible role in treatment of asthma.

ETHNOPHARMACOLOGICAL RELEVANCE: Seed kernel of the plant Ceasalpinia bonducella Linn (Caesalpiniacaeae) are used for the treatment of asthma in folk medicine and ancient books. AIM OF STUDY: To assess the pharmacological efficacy of the plant in asthma and to confine and describe the synthetic constituents from the seeds that are in charge of the action. MATERIAL AND METHODS: The viability of petroleum ether, ethanol extract and ethyl acetate fraction from ethanol extract of C. bonducella seeds were screened for the treatment of asthma by various methods viz. effect of test drug on clonidine and haloperidol induced catalepsy, milk-induced leukocytosis and eosinophilia, mast cell stabilizing activity in mice and studies on smooth muscle preparation of guinea pig ileum (in-vitro). Column chromatography of active extract was done to pinpoint the active compound followed by structure elucidation by FTIR, GCMS and NMR spectroscopic methods. RESULTS: Ethyl acetate fraction from ethanol extract of C. bonducella seeds exhibited antihistaminic activity at the dose of 50 and 100 mg/kg, inhibited clonidine-induced catalepsy but not haloperidol-induced catalepsy. Ethyl acetate fraction from ethanol extract significantly inhibited increased leukocyte and eosinophil count due to milk allergen and showed maximum protection against mast cell degranulation by clonidine. The results of guinea pig ileum indicated that the compound 2 methyl, 1 hexadecanol isolated from ethyl acetate fraction of ethanol extract relaxed significantly the ileum muscle strips pre-contracted by which suggests the involvement of ß2-agonists on the relaxation of the tissue. All the results are dose dependent. Active ethyl acetate fraction from ethanol extract showed presence of anti-asthmatic compound, 2-methyl, 1-hexadecanol. CONCLUSION: The ethyl acetate fraction from ethanol extract of seeds of the plant C. bonducella can inhibit parameters linked to asthma disease.

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.

Ameliorative effects of Artemisia pallens in a murine model of ovalbumin-induced allergic asthma via modulation of biochemical perturbations.

INTRODUCTION: Asthma is a chronic, heterogeneous airway disorder characterized by airway inflammatory and remodeling. Artemisia pallens has been reported to possess antioxidant, anti-inflammatory and Anti-allergic potential. OBJECTIVE: To evaluate the anti-asthmatic effects of methanolic extract of Artemisia pallens (APME) against ovalbumin (OVA)-induced airway hyperresponsiveness (AHR) in rats. MATERIALS AND METHOD: AHR was induced in male Sprague-Dawley rats (180-200g) by intraperitoneal (i.p.) injection of OVA and boosted with an identical OVA solution (s.c.) on day 7. Rats were either treated orally with vehicle (10mg/kg), montelukast (10mg/kg) or APME (100, 200 and 400mg/kg) for next 28days. At the end treatments, various biochemical, molecular (RT-PCR and ELISA analysis) and histological parameters were evaluated. RESULTS: APME (200 and 400mg/kg) significantly attenuated (p<0.05) OVA-induced alteration in lung functions measured by Whole-body plethysmography. Increased Bronchoalveolar Lavage (BAL) fluid differential cell count, as well as total protein and albumin in BAL fluid and lungs, was significantly decreased (p<0.05) by APME. It also significantly attenuated (p<0.05) elevated lung oxido-nitrosative stress, myeloperoxidase, and serum IgE levels. OVA-induced down-regulation in lung Nrf2 and upregulation in TNF-α, IL-1ß, IL-4, IL-6, TGF-ß mRNA expression was significantly attenuated (p<0.05) by APME (200 and 400mg/kg) treatment. Histopathological analysis of lung tissue showed that APME treatment reduced OVA-induced inflammatory influx and fibrosis. CONCLUSION: Artemisia pallens simultaneously orchestrate plethora of mechanisms viz. modulations of IgE, TGF-ß, TNF-α, IL's and Nrf-2 levels to exhibit its anti-asthmatic potential in OVA-induced AHR in rats.

Uncovering the Molecular Mechanism of Anti-Allergic Activity of Silkworm Pupa-Grown Cordyceps militaris Fruit Body.

Cordyceps militaris has been widely used as an herbal drug and tonic food in East Asia and has also been recently studied in the West because of its various pharmacological activities such as antitumoral, anti-inflammatory and immunomodulatory effects. In this study, we examined the molecular mechanism underlying the anti-allergic activity of ethanol extract prepared from silkworm pupa-cultivated Cordyceps militaris fruit bodies in activated mast cells. Our results showed that ethanol extract treatment significantly inhibited the release of [Formula: see text]-hexosaminidase (a degranulation marker) and mRNA levels of tumor necrosis factor-[Formula: see text] as well as interleukin-4 in RBL-2H3 cells. The cells were sensitized with 2,4-dinitrophenol specific IgE and then stimulated with human serum albumin conjugated with 2,4-dinitrophenol. Oral administration of 300[Formula: see text]mg/kg ethanol extract significantly ameliorated IgE-induced allergic reaction in mice with passive cutaneous anaphylaxis. Western immunoblotting results demonstrated that ethanol extract incubation significantly inhibited Syk/PI3K/MEKK4/JNK/c-jun biochemical cascade in activated RBL-2H3 cells, which activated the expression of various allergic cytokines. In addition, it suppressed Erk activation and PLC[Formula: see text] evocation, which would respectively evoke the synthesis of lipid mediators and Ca[Formula: see text] mobilization to induce degranulation in stimulated RBL-2H3 cells. A compound, identified as [Formula: see text]-sitostenone, was shown to inhibit [Formula: see text]-hexosaminidase secretion from activated mast cells. Our study demonstrated that ethanol extract contained the ingredients, which could inhibit immediate degranulation and de novo synthesis of allergic lipid mediators and cytokines in activated mast cells.