Leaves and pseudostems extract of Curcuma longa attenuates immunoglobulin E/bovine serum albumin-stimulated bone marrow-derived cultured mast cell activation and passive cutaneous anaphylaxis in BALB/c mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Curcuma longa, known as turmeric, is an herbaceous perennial plant belonging to the genus Curcuma. It is dispersed throughout tropical and subtropical regions worldwide. Since ancient times, turmeric has been used as an ethnomedicinal plant in the Ayurvedic system, particularly in Asian countries. Rhizomes of turmeric possess several pharmacological properties that give high value as a medicinal remedy for treating a range of conditions, including inflammation, pain, allergies, and digestive issues. Moreover, turmeric leaves and pseudostems also contain a variety of health-enhancing secondary metabolites, such as curcumin, flavonoids, and other phenolic compounds, which exhibit anti-inflammatory, antitumor, antibacterial, and antioxidant properties. AIM OF THE STUDY: Allergic diseases are a group of immune-mediated disorders mainly caused by an immunoglobulin E (IgE)-dependent immunological response to an innocuous allergen. Therefore, this study aimed to investigate the effect of leaves and pseudostems extract of turmeric (TLSWE-8510) on IgE/bovine serum albumin (BSA)-stimulated allergic responses in mouse bone marrow-derived cultured mast cells (BMCMCs) and passive cutaneous anaphylaxis (PCA) in BALB/c mice. MATERIALS AND METHODS: The effect of TLSWE-8510 on mast cell degranulation has been evaluated by investigating the release of ß-hexosaminidase and histamine in IgE/BSA-stimulated BMCMCs. Additionally, anti-allergic properties of TLSWE-8510 on IgE/BSA-stimulated BMCMCs were investigated using suppression of nuclear factor-kappa B (NF-κB), and spleen tyrosine kinase (Syk)-linker for T-cell activation (LAT)-extracellular-signal-regulated kinase (ERK)-GRB2 associated binding protein 2 (Gab2) signaling pathway and downregulation of allergy-related cytokines and chemokines expression. Furthermore, in vivo, studies were conducted using IgE-mediated PCA in BALB/c mice. RESULTS: TLSWE-8510 treatment significantly inhibited the degranulation of IgE/BSA-stimulated BMCMCs by inhibiting the release of ß-hexosaminidase and histamine dose-dependently. Additionally, TLSWE-8510 reduced the expression of high-affinity IgE receptors (Fc epsilon receptor I-FcεRI) on the surface of BMCMCs and the binding of IgE to FcεRI. Besides, the expression of cytokines and chemokines is triggered by IgE/BSA stimulation via activating the allergy-related signaling pathways. TLSWE-8510 dose-dependently downregulated the mRNA expression and the production of allergy-related cytokines (interleukin (IL)-1ß, IL-3, IL-4, IL-5, IL-6, IL-13, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ), and chemokines (thymus and activation-regulated chemokine (TARC), and regulated upon activation, normal T cell expressed and secreted (RANTES)) by regulating the phosphorylation of downstream signaling molecules, NF-κB, and Syk, LAT, ERK and Gab2 in IgE/BSA-stimulated BMCMCs. Moreover, PCA reaction in IgE/BSA-stimulated BALB/c mice ears was effectively decreased by TLSWE-8510 treatment in a dose-dependent manner. CONCLUSIONS: These results collectively demonstrated that TLSWE-8510 suppressed mast cell degranulation by inhibiting the release of chemical mediators related to allergies. TLSWE-8510 downregulated the allergy-related cytokines and chemokines expression and phosphorylation of downstream signaling molecules in IgE/BSA-stimulated BMCMCs. Furthermore, in vivo studies with IgE-mediated PCA reaction in the BALB/c mice ears were attenuated by TLSWE-8510 treatment. These findings revealed that TLSWE-8510 has the potential as a therapeutic agent for the treatment of allergic diseases.

Case Report: Antifungal Agents in the Treatment of Asthma and Allergy After Water-Damaged Building Exposure.

Damp and moisture-damaged building exposure has been linked to adverse health effects, primarily related to respiratory complications from mold spore reactions. This paper describes a case of a previously healthy man who was exposed to a home with hidden mold infestation and remained symptomatic following proper remediation. The patient presented with allergies, allergic bronchopulmonary aspergillosis, and treatment resistant asthma, as well as other non-respiratory symptoms likely related to inhalational mycotoxin exposure from his home. In this case, the addition of systemic and intranasal antifungals improved both respiratory and non-respiratory symptoms. Antifungals were used for a longer duration than customary and in combination with factors that addressed drug resistance.

Traditional Chinese Herbal Medicine for Allergic Diseases: A Review.

The prevalence of allergic disorders has increased in recent years, lowering patients' quality of life and increasing the demand for drugs to treat these diseases. Western drugs such as glucocorticoids, antihistamines, and leukotrienes are routinely utilized in clinics. However, drawbacks like high recurrence rates and adverse effects limit their use. As one of the most promising natural medicine systems, traditional Chinese medicine offers distinct benefits in treating allergic illnesses, such as maintaining long-term treatment, preventing disease recurrence, and producing fewer adverse reactions. We analyzed and discussed recent developments in traditional Chinese medicine used in allergic diseases from three perspectives: Chinese herbal formula, Chinese patent medicine, and active ingredients of traditional Chinese medicine, and explained their main components, efficacy, and mechanisms of action. We also reviewed the modification of Chinese herbal formulas and the combined application of Chinese medicine with Western medicine or nonpharmaceutical therapies. Traditional Chinese medicines are becoming increasingly important in treating allergic disorders. Improving traditional Chinese herbal formulas and developing safe and effective Chinese patent medicines are currently the most pressing and important aspects of research on traditional Chinese medicine.

An overview of penicillin allergies for nurses.

ABSTRACT: Antibiotics are frequently reported as allergies by patients, particularly antibiotics from the penicillin family. Most of these reported allergies are benign, and the consequences of alternative therapies can be significant. This article provides background information on penicillin allergies and serves as a guide to penicillin allergy management.Reprinted with permission from Wrynn, A.F. An overview of penicillin allergies for nurses. Nurse Pract 2022; 47(9): 30-36. Copyright Wolters Kluwer. All rights reserved.

Modulation of the Immune Response to Allergies Using Alternative Functional Foods.

Modulation of the allergic immune response through alternative therapies is a field of study that aims to address allergic reactions differently from traditional approaches. These therapies encompass the utilization of natural functional foods, which have been observed to exert an influence on the immune response, thus mitigating the severity of allergies. Indeed, some studies suggest that the incorporation of these nutraceuticals can regulate immune function, leading to a reduction in histamine release and subsequent alleviation of allergic symptoms. Moreover, certain herbs and dietary supplements, such as curcumin, are believed to possess anti-inflammatory properties, which may serve to moderate allergic responses. Although the results remain somewhat mixed and require further research, these alternative therapies exhibit the potential to impact the allergic immune response, thereby providing complementary options to conventional treatments. Therefore, in this review, we aim to provide an updated account of functional foods capable of modulating the immune response to allergies. In that sense, the review delves into functional foods sourced from plants (phytochemicals), animals, and marine algae. Emphasis is placed on their potential application in the treatment of allergic disorders. It also provides an overview of how these foods can be effectively utilized as functional foods. Additionally, it explores the molecular mechanisms and scientific validity of various bioactive natural compounds in the management of allergies.

A Comprehensive Overview of Allergen-specific Immunotherapy Types, Recombinant and Natural Extract Allergens in the Diagnosis and Treatment of Allergies.

Allergen-specific immunotherapy (AIT) involves administering allergen extracts. It is used to desensitize allergic patients. Herbal allergen extracts that are optimum in efficacy and fewest in side effects are still challenging to produce. To overcome these limitations, oral immunotherapy, epicutaneous immunotherapy, intralymphatic immunotherapy, and artificial recombinant allergen preparations have been evaluated. Recombinant allergens have become more popular with the development of molecular diagnostics and therapeutics. Besides food and drug allergens, pollen, fungal spores, and other allergens have been studied. Based on related clinical studies, this comprehensive overview will present the latest perspectives on AIT methods and available allergenic products, as well as discuss the challenges and opportunities for treating allergic disorders.

Recent advances in improving intranasal allergen-specific immunotherapy; focus on delivery systems and adjuvants.

Allergen-specific Immunotherapy (AIT) is the main therapeutic strategy to control and treat allergic disorders. Intranasal Immunotherapy (INIT) was introduced as a needle-free, noninvasive, and efficient approach among various routes of allergen administration. Since direct exposure of nasal mucosa to allergen extracts could induce local and systemic reactions, recent studies focus on establishing novel formulations using various delivery systems and adjuvants to improve INIT efficacy. This review categorizes and describes natural and synthetic micro/nanoparticles such as chitosan, PLGA, liposome, exosome, and nano-emulation droplets used as delivery systems or immunomodulatory and immune-regulatory agents. Also, multiple microbial agents, including probiotics, mycobacterial and viral components, TLR ligands, and biologic agents, i.e., antibody fragments, recombinant cytokines, vitamin A, and pulsed dendritic cells (DCs), are other platforms that are discussed. In addition, future perspectives and proposed strategies to help INIT were provided.

Therapeutic potency of curcumin for allergic diseases: A focus on immunomodulatory actions.

In light of increasing research evidence on the molecular mechanisms of allergic diseases, the crucial roles of innate and acquired immunity in the disease's pathogenesis have been well highlighted. In this respect, much attention has been paid to the modulation of unregulated and unabated inflammatory responses aiming to suppress pathologic immune responses in treating allergic diseases. One of the most important natural compounds with a high potency of immune modulation is curcumin, an active polyphenol compound derived from turmeric, Curcuma longa L. Curcumin's immunomodulatory action mainly arises from its interactions with an extensive collection of immune cells such as mast cells, eosinophils, epithelial cells, basophils, neutrophils, and lymphocytes. Up to now, there has been no detailed investigation of curcumin's immunomodulatory actions in allergic diseases. So, the present review study aims to prepare an overview of the immunomodulatory effects of curcumin on the pathologic innate immune responses and dysregulated functions of T helper (TH) subtypes, including TH1, TH2, TH17, and regulator T cells (Tregs) by gathering evidence from several studies of In-vitro and In-vivo. As the second aim of the present review, we also discuss some novel strategies to overcome the limitation of curcumin in clinical use. Finally, this review also assesses the therapeutic potential of curcumin regarding its immunomodulatory actions in allergic diseases.

Sword Bean (Canavalia gladiata) Pod Exerts Anti-Allergic and Anti-Inflammatory Effects through Modulation of Th1/Th2 Cell Differentiation.

Allergy is an immunoglobulin E (IgE)-mediated process, and its incidence and prevalence have increased worldwide in recent years. Therapeutic agents for allergic diseases are continuously being developed, but side effects follow when used for a long-term use. Therefore, treatments based on natural products that are safe for the body are urgently required. Sword bean (Canavalia gladiata) pod (SBP) has been traditionally used to treat inflammatory diseases, but there is still no scientific basis for its anti-allergic effect. Accordingly, this study investigates the anti-allergic effect and its mechanism of SBP in vitro and in vivo. SBP reduced the nitric oxide production and decreased mRNA and protein expression of inflammatory mediates (inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2)), and inhibited the phosphorylation of nuclear factor kappa B (NF-κB), a major signaling molecule in the inflammatory response. Additionally, SBP extract treatment inhibited phosphatidylinositol-3-kinase/mammalian target of rapamycin (PI3K/mTOR) signaling activity to further inhibit degranulation and allergy mediator generation and control the balance of Th1/Th2 cells, which can induce an allergic reaction when disrupted. Furthermore, the SBP extract exhibited anti-allergic effects in anti-dinitrophenyl IgE-induced RBL-2H3 cells and ovalbumin-treated mice. These findings have potential clinical implications for the treatment as well as prevention of allergic diseases.

Anti-pseudo-allergic components in licorice extract inhibit mast cell degranulation and calcium influx.

Pseudo-allergic reactions (PARs) widely occur upon application of drugs or functional foods. Anti-pseudo-allergic ingredients from natural products have attracted much attention. This study aimed to investigate anti-pseudo-allergic compounds in licorice. The anti-pseudo-allergic effect of licorice extract was evaluated in rat basophilic leukemia 2H3 (RBL-2H3) cells. Anti-pseudo-allergic compounds were screened by using RBL-2H3 cell extraction and the effects of target components were verified further in RBL-2H3 cells, mouse peritoneal mast cells (MPMCs) and mice. Molecular docking and human MRGPRX2-expressing HEK293T cells (MRGPRX2-HEK293T cells) extraction were performed to determine the potential ligands of MAS-related G protein-coupled receptor-X2 (MRGPRX2), a pivotal target for PARs. Glycyrrhizic acid (GA) and licorice chalcone A (LA) were screened and shown to inhibit Compound48/80-induced degranulation and calcium influx in RBL-2H3 cells. GA and LA also inhibited degranulation in MPMCs and increase of histamine and TNF-α in mice. LA could bind to MRGPRX2, as determined by molecular docking and MRGPRX2-HEK293T cell extraction. Our study provides a strong rationale for using GA and LA as novel treatment options for PARs. LA is a potential ligand of MRGPRX2.

Neobavaisoflavone inhibits allergic inflammatory responses by suppressing mast cell activation.

Neobavaisoflavone (NBIF), a monomolecular compound extracted from Psoralea corylifolia (Leguminosae), is commonly used in traditional Chinese medicine for multiple purposes. NBIF is known to exert anti-fungal and anti-tumor effects, and promote bone formation. Whether NBIF exhibits anti-allergic effects by regulating mast cell activation remains unclear. Therefore, we designed this study to investigate the anti-allergic effects of NBIF on IgE/Ag-induced mouse bone marrow-derived mast cells and ovalbumin-induced asthma, and the passive systemic anaphylaxis (PSA) reaction in mice. Our results showed that NBIF suppresses the production of leukotriene C4, prostaglandin D2 and inflammatory cytokines, and decreases the degranulation of BMMCs stimulated by IgE/Ag. A thorough investigation ascertained that NBIF suppresses the phosphorylation of mitogen-activated protein kinases, and represses the nuclear factor-κB-related signaling pathway. In addition, the oral administration of NBIF in mice inhibited the IgE-induced PSA reaction in a dose-dependent manner. Overall, we provide new insights into how NBIF regulates the IgE/Ag-mediated signaling pathways. Moreover, our investigation promotes the potential use of NBIF in treating allergy and asthma.

Effect of Loaded Glycyrrhizic Acid on PLGA Nano-particle on Treatment of Allergic Asthma.

Asthma is considered a complex disease of the respiratory system that is characterized by bronchoconstriction, airway inflammation, cough, dyspnea, and wheezing. Allergic reactions are the main reason behind asthma which is known as an important health problem with a high rate of morbidity and mortality in patients with respiratory diseases. Liquorice, the root of Glycyrrhiza, is primarily effective for asthma which is widely used in herbal medicine. In the present study, we designed nano-particles that carry Glycyrrhizic acid as the effective component of Liquorice. After Poly (D,L-lactide-co-glycolic acid) PLGA nanoparticle preparation and Glycyrrhizic acid loading, the morphology of the nanoparticle, the electric charge distribution, and drug-releasing ability were studied. Then the effect of Glycyrrhizic acid-PLGA on the animal model of allergic asthma was investigated. Glycyrrhizic acid-nanoparticle had a mean±SD size of 350±50 nm. about 67% of the effective component was released after 10 h. The interleukin (IL)-4, IL-5, IL-13, and IL-25 levels and the Muc5ac mRNA expression were decreased in the Glycyrrhizic acid-PLGA treated group. In addition, a significant decline was observed in goblet cell hyperplasia, mucus hyper-secretion, and eosinophilic inflammation around bronchi and vessels of the nano-drug treated group, compared with the asthmatic group. We found that Glycyrrhizic acid-PLGA nanoparticle had an anti-asthma effect which may be used as a new drug to cure asthma. It can prevent bronchial obstruction, breathlessness, and asthma attacks.

Resveratrol Attenuates Mast Cell Mediated Allergic Reactions: Potential for Use as a Nutraceutical in Allergic Diseases?

Allergic diseases are one of the most common health disorders affecting about 30% of the world population. Mast cells (MCs) are key effector cells of allergic reactions by releasing proinflammatory mediators including histamine, lipid mediators, and cytokines/chemokines. Natural substances like secondary plant substances such as resveratrol (RESV), which can contribute to prevention and treatment of diseases, are becoming increasingly interesting for use as nutraceuticals. In this review, the anti-inflammatory effects of RESV on MC-mediated allergic reactions in vitro and in vivo models are summarized. The studies indicate that RESV inhibits MC degranulation, synthesis of arachidonic acid metabolites, expression of cytokines and chemokines as well as activation of signal molecules involved in proinflammatory mechanisms. Also, beneficial impacts by this polyphenol are reported in randomized controlled trials with allergic rhinitis patients. Although it cannot yet be concluded that RESV can be used successfully in allergy patients in general, there are many results that indicate a possible role for RESV for use as an anti-inflammatory nutraceutical. However, strategies to favorably influence the poor bioavailability of RESV would be helpful.

Mitomycin C allergy after passive and device-assisted hyperthermia for non-muscle invasive bladder cancer treatment: A retrospective cohort from a high-volume center.

INTRODUCTION: Mitomycin C (MMC) is one of the most frequently utilized intravesical chemotherapy drugs for the management of non-muscle-invasive bladder cancer (NMIBC). Allergic reactions (Type 4 delayed hypersensitivity) are seldomly reported in the literature but not so infrequent in daily practice, its incidence has been increasing with the use of device-assisted hyperthermia. This study aims to identify the incidence, risk factors, and clinical characteristics of patients with allergic reactions to MMC. PATIENTS AND METHODS: Single-center retrospective cohort from June 2014 to August 2018. Patients with intermediate or high-risk NMIBC were included. Patients received passive MMC (4 weekly and eleven monthly instillations of 40mg of MMC) or Chemohyperthermia (CHT) with MMC (6 weekly and 6-monthly instillations, heated at 43°C [+/- 0.5°C] using Combat BRS). RESULTS: We included 258 patients (MMC = 157, CHT = 101) and found 7 (4.4%) suspected and 4 confirmed (2.4%) allergies in the passive MMC group and 11 suspected (10.9%) and 7 confirmed (6.9%) in the CHT group. The mean number of instillations received before developing the allergy was 6 in the passive MMC and 5 in the CHT group. Seven out of 18 suspected allergy cases were pseudo-allergic reactions with negative allergy tests. Early postoperative MMC instillation was associated with an increased risk of allergy (OR 2.47 [CI 1.39-4.36], P = 0.001), while neither history of atopy nor history of other medications allergy was found to increase the risk. CONCLUSION: MMC allergy risk is increased with the use of device-assisted hyperthermia with an incidence of 2.4% for passive MMC and 6.9% for CHT. History of prior allergies does not seem to increase the risk of developing MMC allergy. In this series 38% of suspected cases were found to be pseudo-allergic reactions, highlighting the need to confirm the diagnosis before definitively stopping the treatment.

Natural Anti-inflammatory and Anti-allergy Agents: Herbs and Botanical Ingredients.

Allergies have been known to be an abnormally vigorous immune response in which the immune system fights off an allergen or antigen, initiating mast cells to release histamine into the blood. Substances that prevent mast cells from releasing histamine are considered antiallergic agents. The drugs utilized to treat allergy are mast cell stabilizers, steroids, anti-histamine, leukotriene receptor antagonists, and decongestants. Anti-histamine drugs have side effects such as drowsiness, confusion, constipation, difficulty urinating, blurred vision, etc. The use of medicinal plants for the effective and safe management of diseases has recently received much attention. Various herbs are utilized for their antiallergic and anti-histaminic properties. Some of the herbs useful in the management of allergic diseases of the respiratory tract, like Piper longum, Ocimum tenuiflorum, Solanum xanthocarpum have been discussed. Ample scientific evidence is available for the anti-histaminic and antiallergic activity of Azadirachta indica, Aloe vera, Tinospora cordifolia, and many other such herbs are safer to use as antiallergic agents have been reported. The review summarizes a wide variety of herbs and botanical ingredients with their common scientific names and distribution for easy identification and usage as safe antiallergic agents and discusses their molecular mechanisms involved in combating allergic reactions.

Dehydroandrographolide targets CD300f and negatively regulated MRGPRX2-induced pseudo-allergic reaction.

Mas-related G protein-coupled receptor X2 (MRGPRX2) mediates mast cells (MCs) activation, which is a key target for the treatment of allergic diseases. However, there are few drugs targeting MRGPRX2. Leukocyte mono-immunoglobulin-like receptor 3 (CD300f) is a negative regulator of FcεRΙ-mediated MC activation. However, the regulatory effect of CD300f on MRGPRX2 remains unclear. Dehydroandrographolide (DA) is a main contributor of Andrographis paniculata (Burm.f.) Nees (family: Acanthaceae) have been shown to inhibit type I hypersensitivity. The aim of this study was to determine whether DA negatively regulated MRGPRX2-mediated MC activation via CD300f and showed therapeutic effect on pseudo-allergic reactions. Mouse allergic models and MC degranulation were detected in vivo and in vitro, and inflammatory mediators were detected. siRNA interference and Biacore were used to verify the target. DA inhibited pseudo-allergic reactions by reducing vasodilation and serum cytokine levels in mice and inhibited MRGPRX2-mediated MC activation. The regulatory effect of DA was significantly decreased after the knockdown of CD300f expression. Moreover, DA upregulated the phosphorylation level of Src homology region 2 domain-containing phosphatase (SHP)-1 and SHP-2, which are key kinases in the negative regulatory signaling pathways associated with CD300f. In conclusion, DA negatively regulates MRGPRX2-mediated MC activation via CD300f to inhibit pseudo-allergic reactions.

Postoperative anti-inflammatory efficacy of 2% saline rinses and a herbal- mouthwash after non-surgical periodontal therapy for the management of periodontal inflammation in young adults with chlorhexidine allergy: A randomized controlled trial.

AIM: The present randomized controlled trial assessed the postoperative anti-inflammatory efficacy of 2% saline rinses (SR) and a herbal- mouthwash (HMW) after non-surgical periodontal therapy (NSPT) for the management of periodontal inflammation in patients with chlorhexidine (CHX) allergy. MATERIALS AND METHODS: Patients with periodontal inflammation with and without self-reported CHX allergy were included. All patients underwent non-surgical periodontal therapy (NSPT). Patients were randomly divided into three groups. In the SR and HMW groups, 2% SR and a HMW, respectively, were prescribed. In Group 3 (CHX-group), patients without CHX allergy were included and were prescribed 0.12% CHX. In all groups, plaque index (PI), gingival index (GI), probing depth (PD), clinical attachment loss (AL), and marginal bone loss were measured at baseline. Clinical periodontal parameters were re-assessed at 6-weeks' follow-up. p < 0.01 were considered statistically significant. RESULTS: Thirteen, 12, and 12 patients were included in the SR, HMW, and CHX groups, respectively. At baseline, clinical and radiographic periodontal parameters were comparable in all groups. In all groups, PI (p < 0.01), GI (p < 0.01), and PD (p < 0.01) were significantly higher at baseline than their respective values at 6 weeks of follow-up. There was no significant difference in clinical AL at all time intervals in all groups. There was no significant correlation between periodontal parameters and age, gender, and daily toothbrushing/flossing in all groups. CONCLUSION: In young adults with self-reported CHX allergy, herbal mouthwashes and/or 2% SR are suitable post-operative prescriptions after NSPT.

Patho-Pharmacological Research of Anti-allergic Natural Products Targeting Antihistamine-Sensitive and -Insensitive Allergic Mechanisms.

Histamine H1 receptor (H1R) has a special up-regulation mechanism by the stimulation of H1R, mediated by protein kinase C-delta (PKCδ) signaling and H1R gene expression, resulting increase in H1R signaling. Increase in H1R mRNA in nasal mucosa was induced after the provocation of nasal hypersensitivity model rats and suppressed by the pre-treatment of antihistamines. Improvement of nasal symptoms and suppression of H1R mRNA expression in nasal mucosa were also observed by the pre-treatment of antihistamines in pollinosis patients. Elucidation of a correlation between symptoms and H1R mRNA level suggests that H1R gene is an allergic disease (AD)-susceptibility gene, targeted by antihistamines. Similar to antihistamines, pre-treatment of Kujin extract, an anti-allergic Kampo medicine improved nasal symptoms and suppressed H1R mRNA expression in nasal hypersensitivity model rats. (-)-Maackiain targeting heat shock protein 90 (Hsp90) was isolated as an inhibitor of PKCδ signaling-mediated H1R gene expression from Kujin extract. In addition to H1R-mediated activation of H1R gene expression as the first mechanism, nuclear factor of activated T-cells (NFAT)-mediated IL-9 gene expression is suggested to participate to allergic symptoms as the second mechanism insensitive to antihistamines. Pyrogallol and proanthocyanidin suppressing IL-9 gene expression were discovered from Awa-tea and lotus root knots, respectively. Combination therapy using medicines suppressing both H1R gene expression and IL-9 gene expression is promising for outstanding alleviation of AD. Multifactorial diseases involving H1R gene expression may be treated by the combination therapy with antihistamine and complementary drugs, and diseases involving PKCδ signaling may be treated by drugs targeting Hsp90.

Anti-pseudo-allergic components in licorice extract inhibit mast cell degranulation and calcium influx / 中国天然药物

Pseudo-allergic reactions (PARs) widely occur upon application of drugs or functional foods. Anti-pseudo-allergic ingredients from natural products have attracted much attention. This study aimed to investigate anti-pseudo-allergic compounds in licorice. The anti-pseudo-allergic effect of licorice extract was evaluated in rat basophilic leukemia 2H3 (RBL-2H3) cells. Anti-pseudo-allergic compounds were screened by using RBL-2H3 cell extraction and the effects of target components were verified further in RBL-2H3 cells, mouse peritoneal mast cells (MPMCs) and mice. Molecular docking and human MRGPRX2-expressing HEK293T cells (MRGPRX2-HEK293T cells) extraction were performed to determine the potential ligands of MAS-related G protein-coupled receptor-X2 (MRGPRX2), a pivotal target for PARs. Glycyrrhizic acid (GA) and licorice chalcone A (LA) were screened and shown to inhibit Compound48/80-induced degranulation and calcium influx in RBL-2H3 cells. GA and LA also inhibited degranulation in MPMCs and increase of histamine and TNF-α in mice. LA could bind to MRGPRX2, as determined by molecular docking and MRGPRX2-HEK293T cell extraction. Our study provides a strong rationale for using GA and LA as novel treatment options for PARs. LA is a potential ligand of MRGPRX2.

Suppression on allergic airway inflammation of dehulled adlay (Coix lachryma-jobi L. var. ma-yuen Stapf) in mice and anti-degranulation phytosterols from adlay bran.

Adlay (Coix lachryma-jobi L. var. ma-yuen Stapf) seeds have been used in Asia for thousands years to treat warts, chapped skin, rheumatism, and neuralgia. The anti-allergic activity of dehulled adlay (DA) seeds was identified, and the bran (AB) is regarded as the main functional constituent in the edible part. However, no study has focused on in vivo acute anti-allergic airway inflammation. In the present report, we investigated DA methanolic extract (DAM) reversed ovalbumin (OVA)/methacholine (Mch)-induced airway hypersensitivity, decreased interleukin (IL)-4, IL-5, and IL-13 levels from splenocytes, suppressed tumor necrosis factor (TNF)-α, IL-1ß, and IL-13 levels and reduced eosinophil counts and eotaxin in bronchoalveolar lavage fluid (BALF), which imply that the modulatory effects of DA should involve allergic degranulation. Further, seven phytosterols were isolated from AB ethanolic extract (ABE); among them, 3-O-caffeoyl-5ß-sitostan-3-ol, ß-sitosterol 3-O-glucopyranoside and ß-sitosterol inhibited ß-hexosaminidase release from A23187-stimulated RBL-2H3 cells with percentages of 54.1%, 52.0% and 48.5%, respectively, at 50 µM. In addition, ß-sitosterol reduced immunoglobulin (Ig)E-stimulated degranulation on RBL-2H3 cells in a dose-dependent manner. The phytosterols were the predominant components based on gas chromatography (GC) analysis. This is the first study to demonstrate that DA suppressed OVA/Mch-induced acute airway inflammation. The phytosterols in AB showed significant anti-degranulation activities, and may be regarded as the indicative components of AB for anti-allergy effects.