Ameliorative effects of Wikstroemia trichotoma 95% EtOH extract on a mouse model of DNCB-induced atopic dermatitis.

ETHNOPHARMACOLOGICAL RELEVANCE: The genus Wikstroemia has been extensively utilized in traditional Chinese medicine (TCM) for the management of conditions such as coughs, edema, arthritis, and bronchitis. Studies have indicated that the crude extracts of Wikstroemia exhibit anti-inflammatory, anti-allergy, anti-aging, skin psoriasis, anti-cancer, and antiviral properties. In addition, these extracts are known to contain bioactive substances, including flavonoids, coumarins, and lignans. However, few studies have investigated the anti-inflammatory or anti-allergic activities of Wikstroemia trichotoma (Thunb.) Makino against atopic dermatitis (AD). AIM OF THE STUDY: The study aimed to explore the potential of a 95% ethanol extract of W. trichotoma (WTE) on the dysfunction of skin barrier and immune system, which are primary symptoms of AD, in 2,4-dinitrochlorobenzene (DNCB)-induced SKH-1 hairless mice and phorbol 12-myristate 13-acetate (PMA)/ionomycin or immunoglobulin E (IgE) + 2,4-dinitrophenylated bovine serum albumin (DNP-BSA) stimulated rat basophilic leukemia cell line (RBL-2H3). Furthermore, we sought to identify the chemical contents of WTE using high-performance liquid chromatography equipped with a photodiode array detector (HPLC-PDA). MATERIALS AND METHODS: An in vitro study was conducted using RBL-2H3 cells stimulated with PMA/ionomycin or IgE + DNP-BSA to assess the inhibitory effects of WTE on mast cell degranulation and interleukin-4 (IL-4) mRNA expression levels. For the in vivo study, AD was induced in SKH-1 hairless mice by applying 1% DNCB to the dorsal skin daily for 7 days. Subsequently, 0.1% DNCB solution was applied on alternate days, and mice were orally administered WTE (at 30 or 100 mg/kg/day) dissolved in 0.5% carboxymethyl cellulose (CMC) daily for 2 weeks. Transepidermal water loss (TEWL), skin hydration, skin pH, and total serum IgE levels were measured. RESULTS: In DNCB-stimulated SKH-1 hairless mice, WTE administration significantly improved AD symptoms and ameliorated dorsal skin inflammation. Oral administration of WTE led to a significant decrease in skin thickness, infiltration of mast cells, and level of total serum IgE, thus restoring skin barrier function in the DNCB-induced skin lesions. In addition, WTE inhibited ß-hexosaminidase release and reduced IL-4 mRNA levels in RBL-2H3 cells. Chemical profile analysis of WTE confirmed the presence of three phenolic compounds, viz. chlorogenic acid, miconioside B, and matteucinol-7-O-ß-apiofuranosyl (1 â†’ 6)-ß-glucopyranoside. CONCLUSIONS: WTE ameliorates AD symptoms by modulating in the skin barrier and immune system dysfunction. This suggests that W. trichotoma extract may offer therapeutic benefits for managing AD.

Shiikuwasha leaf and peel extracts inhibit allergic reactions by suppressing degranulation in RBL-2H3 rat basophilic leukemia cells and immunoglobulin production in mouse spleen lymphocytes.

This study aims to investigate the antiallergic effects of Shiikuwasha (Citrus depressa Hayata) leaf and peel extracts by examining the regulation of degranulation and inflammatory cytokine production from rat basophilic leukemia (RBL-2H3) cells and antigen-specific antibody production in sensitized mouse spleen lymphocytes. In vivo antiallergic activity was evaluated using the passive cutaneous anaphylaxis (PCA) reaction model. Extracts of Shiikuwasha leaves and peel were prepared using 80% methanol and dissolved in dimethylsulfoxide. The dinitrophenyl-human serum albumin-induced ß-hexosaminidase levels in immunoglobulin (Ig) E-sensitized RBL-2H3 cells were assessed using enzymatic assays. Cytokine production was measured by enzyme-linked immunosorbent assay. Antibody production capacity was evaluated using lymphocytes isolated from spleens of type I allergy model mice. Lymphocytes were cultured for 72 h with Shiikuwasha extracts, and ovalbumin-specific IgE, IgG1, and IgG2a levels were measured. Shiikuwasha leaf and peel extract significantly reduced ß-hexosaminidase release and suppressed interleukin-4 and tumor necrosis factor-α production from RBL-2H3 cells. Ovalbumin-specific IgE and IgG1 production decreased in Shiikuwasha extract-treated lymphocytes. These extracts also significantly suppressed the PCA reaction. Shiikuwasha leaf and peel extract reduce degranulation in RBL-2H3 cells and antibody production in spleen-derived lymphocytes and therefore exhibit antiallergic effects.

Inhibition of pseudo-allergic reactions by vitamin K3 directly targeting GAB1 in mast cells.

BACKGROUND: Vitamin K3 (VK3), a fat-soluble synthetic analog of the vitamin K family, has coagulant, anti-inflammatory, antibacterial, and anticancer properties. Pseudo allergy is a IgE-independent immune response associated with mast cells. This study investigated the role of VK3 in IgE-independent mast cell activation. METHODS: Substance P (SP) was used to induce LAD2-cell activation in order to analyze the effects of VK3 in vitro. Cutaneous allergy and systemic allergy mouse models were used to analyze the anti-pseudo-allergic effects of VK3. Proteome microarray assays were used to analyze VK3-binding protein. Biolayer interferometry and immunoprecipitation were used to verify interaction between VK3 and its key targets. RNA interference was used to determine the role of GAB1 in LAD2cell activation. RESULTS: VK3 inhibited SP-induced LAD2-cell activation, and resulted in the release of ß-hexosaminidase, histamine and cytokines; VK3 inhibited SP-induced pseudo allergic reactions in mice, and serum histamine and TNF-α levels decreased. Degranulation of skin mast cells was reduced; GAB1 in mast cells was stably bound to VK3. GAB1 participated in SP-induced LAD2-cell activation. GAB1 knockdown in LAD2 cells prevented SP-induced ß-hexosaminidase release, calcium mobilization and cell skeletal remodeling. VK3 directly binds to GAB1 and reduces its expression to inhibited SP-induced LAD2 cell activation. CONCLUSION: The anti-pseudo-allergic activity of VK3 was confirmed in vitro and in vivo. VK3 can inhibit SP-induced mast cell activation by directly targeting GAB1. This study provides new insights on the activity of VK3 and the mechanism of pseudoallergic reaction.

Comparison of anti-allergic activities of different types of lotus seed resistant starch in OVA-induced mouse model.

Currently, evidence from observational studies suggests dietary fiber intake may be associated with decreased risk of food allergy. As a type of dietary fiber, resistant starch was also widely reported to possess anti-allergic properties. However, there is a relative paucity of studies assessing the influence of resistant starch types on their anti-allergic activity and its possible underlying mechanisms. In the current study, the anti-allergic effects of RS3-type (retrograded starch), RS4-type (chemically modified starch, cross-bonded), and RS5-type (starch-palmitic acid complex) of lotus seed resistant starch were evaluated in the OVA (100 mg/kg)-induced food allergic mice model. The results showed that oral administration of RS3 or RS4 lotus seed resistant starch (0.3 g/100 g b.w.) for 25 days significantly improved adverse symptoms of food allergy such as weight loss, increases in allergy symptom score and diarrhea rate; with significant reduction of serum specific antibody IgE, TNF-α, IL-4 levels and improved Th1/Th2 balance being observed. The mechanism may involve the regulation of lotus seed resistant starch on intestinal flora and the metabolites short-chain fatty acids and bile acids. Taken together, the findings may enhance understanding towards ameliorative effects of resistant starch on food allergy, and offer valuable insights for the exploration of novel anti-allergic bioactive compounds.

Inhibitory effect of phellodendrine on C48/80-induced allergic reaction in vitro and in vivo.

The incidence of allergic reactions has risen steadily in recent years, prompting growing interest in the identification of efficacious and safe natural compounds that can prevent or treat allergic diseases. Phellodendron amurense Rupr. has long been applied as a treatment for allergic diseases, whose primary component is phellodendrine. However, the efficacy of phellodendrine as a treatment for allergic diseases remains to be assessed. Mast cells are the primary effectors of allergic reactions, which are not only activated by IgE-dependent pathway, but also by IgE-independent pathways via human MRGPRX2, rat counterpart MRGPRB3. As such, this study explored the effect and mechanism of phellodendrine through this family receptors in treating allergic diseases in vitro and in vivo. These analyses revealed that phellodendrine administration was sufficient to protect against C48/80-induced foot swelling and Evans blue exudation in mice, and suppressed C48/80-induced RBL-2H3 rat basophilic leukemia cells degranulation, and ß-HEX, HIS, IL-4, and TNF-α release. Moreover, phellodendrine could reduce the mRNA expression of MRGPRB3 and responsiveness of MRGPRX2 by altering its structure. It was able to decrease Ca2+ levels, phosphorylation levels of CaMK, PLCß1, PKC, ERK, JNK, p38, and p65, and inhibit the degradation of IκB-α. These analyses indicate that berberine inhibits the activation of PLC and downregulates the release of Ca2+ in the endoplasmic reticulum by altering the conformation of MRGPRB3/MRGPRX2 protein, thereby inhibiting the activation of PKC and subsequently inhibiting downstream MAPK and NF-κB signaling, ultimately suppressing allergic reactions. There may thus be further value in studies focused on developing phellodendrine as a novel anti-allergic drug.

Se-rich tea polysaccharide extracted by high hydrostatic pressure attenuated anaphylaxis by improving gut microbiota and metabolic regulation.

Selenium-rich tea polysaccharides (Se-TPS) were extracted via high hydrostatic pressure technology with a pressure of 400 MPa (200-500 MPa) for 10 min (3-20 min) at a material-to-solvent ratio of 1:40 (1:20-1:50). Subsequently, Se-TPS1-4 were isolated and purified, with Se-TPS3-4 as the main components. A spectral analysis proved that Se, which has antioxidant activity, existed. An in vitro study found that among Se-TPS, Se-TPS3-4 attenuated the release of ß-hexosaminidase, histamine, and interleukin (IL)-4. Furthermore, in vivo experiments revealed that treatment with Se-TPS downregulated IL-4 levels and upregulated TGF-ß and interferon-γ levels to improve imbalanced Th1/Th2 immunity in tropomyosin-sensitized mice. Moreover, Se-TPS promoted Lactobacillus and norank_f_Muribaculaceaek growth and upregulated metabolites such as genipin and coniferyl alcohol. Overall, these results showed the strong anti-allergy potential of Se-TPS by regulating mast cell-mediated allergic inflammatory responses and microbiota regulation, highlighting the potential of Se-TPS as a novel therapeutic agent to regulate allergy-associated metabolic disorders.

Lead Optimization of Butyrolactone I as an Orally Bioavailable Antiallergic Agent Targeting FcγRIIB.

Food allergy (FA) poses a growing global food safety concern, yet no effective cure exists in clinics. Previously, we discovered a potent antifood allergy compound, butyrolactone I (BTL-I, 1), from the deep sea. Unfortunately, it has a very low exposure and poor pharmacokinetic (PK) profile in rats. Therefore, a series of structural optimizations toward the metabolic pathways of BTL-I were conducted to provide 18 derives (2-19). Among them, BTL-MK (19) showed superior antiallergic activity and favorable pharmacokinetics compared to BTL-I, being twice as potent with a clearance (CL) rate of only 0.5% that of BTL-I. By oral administration, Cmax and area under the concentration-time curve (AUC0-∞) were 565 and 204 times higher than those of BTL-I, respectively. These findings suggest that butyrolactone methyl ketone (BTL-BK) could serve as a drug candidate for the treatment of FAs and offer valuable insights into optimizing the druggability of lead compounds.

Fucosterol isolated from Sargassum horneri attenuates allergic responses in immunoglobulin E/bovine serum albumin-stimulated mast cells and passive cutaneous anaphylaxis in mice.

Allergic diseases have become a serious problem worldwide and occur when the immune system overreacts to stimuli. Sargassum horneri is an edible marine brown alga with pharmacological relevance in treating various allergy-related conditions. Therefore, this study aimed to investigate the effect of fucosterol (FST) isolated from S. horneri on immunoglobulin E(IgE)/bovine serum albumin (BSA)-stimulated allergic reactions in mouse bone marrow-derived cultured mast cells (BMCMCs) and passive cutaneous anaphylaxis (PCA) in BALB/c mice. The in silico analysis results revealed the binding site modulatory potential of FST on the IgE and IgE-FcεRI complex. The findings of the study revealed that FST significantly suppressed the degranulation of IgE/BSA-stimulated BMCMCs by inhibiting the release of ß-hexosaminidase and histamine in a dose-dependent manner. In addition, FST effectively decreased the expression of FcεRI on the surface of BMCMCs and its IgE binding. FST dose-dependently downregulated the expression of allergy-related cytokines (interleukin (IL)-4, -5, -6, -13, tumor necrosis factor (TNF)-α, and a chemokine (thymus and activation-regulated chemokine (TARC)) by suppressing the activation of nuclear factor-κB (NF-κB) and Syk-LAT-ERK-Gab2 signaling in IgE/BSA-stimulated BMCMCs. As per the histological analysis results of the in vivo studies with IgE-mediated PCA in BALB/c mice, FST treatment effectively attenuated the PCA reactions. These findings suggest that FST has an immunopharmacological potential as a naturally available bioactive compound for treating allergic reactions.

Vegetable Extracts as Therapeutic Agents: A Comprehensive Exploration of Anti-Allergic Effects.

Food allergies are common worldwide and have become a major public health concern; more than 220 million people are estimated to suffer from food allergies worldwide. On the other hand, polyphenols, phenolic substances found in plants, have attracted attention for their health-promoting functions, including their anti-allergic effects. In this study, we examined the potential inhibitory effects of 80% ethanol extracts from 22 different vegetables on the degranulation process in RBL-2H3 cells. Our aim was to identify vegetables that could prevent and treat type I allergic diseases. We found strong inhibition of degranulation by extracts of perilla and chives. Furthermore, we verified the respective efficacy via animal experiments, which revealed that the anaphylactic symptoms caused by ovalbumin (OVA) load were alleviated in OVA allergy model mice that ingested vegetable extracts of perilla and chives. These phenomena were suggested to be caused by induction of suppression in the expression of subunits that constitute the high-affinity IgE receptor, particularly the α-chain of FcεR I. Notably, the anti-allergic effects of vegetables that can be consumed daily are expected to result in the discovery of new anti-immediate allergenic drugs based on the components of these vegetables.

Anti-allergic effect of vitamin C through inhibiting degranulation and regulating TH1/TH2 cell polarization.

BACKGROUND: Food allergy has become a global public health problem. This study aimed to explore the possible anti-allergic effect of vitamin C (VC). A rat basophilic leukemia (RBL)-2H3 cell degranulation model was used to assess the effect of VC on degranulation in vitro, and an ovalbumin (OVA)-induced BALB/c mouse allergy model was used to assess the anti-allergy effect of VC in vivo. RESULTS: In vitro, VC significantly attenuated the release of ß-hexosaminidase, tryptase and histamine, and also reduced cytokine production (interleukins 4 and 6, tumor necrosis factor α) significantly (P < 0.05), with the inhibitory effect demonstrating a positive correlation with VC dose. In vivo, compared with the OVA group, the levels of serum immunoglobulins E and G1 of the VC low-dose (VCL) group (50 mg kg-1) and high-dose (VCH) group (200 mg·kg-1) were significantly reduced (P < 0.05). Furthermore, the plasma histamine level was also significantly decreased (P < 0.05). Moreover, TH2 cell polarization in mice of the VCL and VCH groups was significantly inhibited (P < 0.05), promoting the TH1/TH2 cell polarization balance. Additionally, VC treatment enhanced the expression of CD80 (P < 0.05) in spleen and small intestine tissues, while significantly inhibiting the expression of CD86 (P < 0.05); notably, high-dose VC treatment was more effective. CONCLUSION: VC exerted an anti-allergic effect through inhibiting degranulation and regulating TH1/TH2 cell polarization balance. © 2024 Society of Chemical Industry.

Crude Polysaccharides from Mushrooms Elicit an Anti-Allergic Effect Against Type 1 Allergy In Vitro.

Type 1 allergic disease is a global challenge, hence the search for alternative therapies. Mushrooms have several medicinal and health benefits. However, scant data exist on the anti-allergic properties of polysaccharides from fruiting bodies (FB) and mycelia of mushrooms. We used an in vitro co-culture system comprising Caco-2 cells (intestinal epithelial colorectal carcinoma cell line) and RBL-2H3 cells (cell line from rat basophilic leukemia cells). Reduction in degranulation of mast cells indicated anti-allergy properties. The inhibitory effect of crude polysaccharides from different mushroom FB and mycelia on ß-hexosaminidase release from RBL-2H3 cells was measured. Results showed that crude polysaccharides from the FB of Inonotus obliquus exhibited a significant inhibitory effect on ß-hexosaminidase release and lowered it by 16%. Polysaccharides from the FB of Lentinus squarrosulus, and Pleurotus ostreatus did not exhibit a significant reduction in ß-hexosaminidase. However, crude polysaccharides from their mycelia had a significant inhibitory effect, resulting in up to a 23% reduction in ß-hexosaminidase activity. Among fungi showing degranulation properties, crude polysaccharides from their mycelia showed more potent action against degranulation than their corresponding FB. Polysaccharides extracted from FB and or mycelia, of selected mushrooms, possess anti-allergic properties that could be harnessed for use in alternative allergy therapies.

Marine-Derived Alternariol Monomethyl Ether Alleviates Ovalbumin-Induced Food Allergy by Suppressing MAPK and NF-κB Signaling Pathways of Mast Cells.

The prevalence of food allergies has grown dramatically over the past decade. Recently, studies have shown the potential of marine substances to alleviate food allergies. We utilized a rat basophilic leukemia (RBL)-2H3 model to evaluate the antiallergic effects of alternariol monomethyl ether (AME) extracted from marine fungi Alternaria sp. Our results showed that AME attenuated food allergy symptoms in mice and reduced histamine release in serum. The population of mast cells in the spleen and mesenteric lymph nodes was considerably reduced. Moreover, in vitro assays also revealed that AME inhibited the release of ß-hexosaminidase and histamine. Transcriptomic analysis uncovered that AME regulated gene expression associated with mast cells. Additionally, Western blotting demonstrated that AME suppressed mast cell activation by modulating MAPK and NF-κB signaling pathways. Taken together, these findings provide a theoretical basis for the potential antiallergic use of marine-derived compounds in the development of functional foods.

Screening of probiotic Lactobacillus to reduce peanut allergy and with potential anti-allergic activity.

BACKGROUND: Peanut is a significant source of nutrition and a valuable oilseed crop. It is also a serious allergy source, which poses a threat to 1.1% of the population. This study aimed to screen lactic acid bacteria (LAB) with the capacity to alleviate peanut allergenicity and exhibit anti-allergic properties. RESULT: The results show that LAB can make use of substances in peanuts to reduce the pH of peanut milk from 6.603 to 3.593-4.500 by acid production and that it can utilize the protein in peanuts to reduce the allergenic content (especially Ara h 1) and improve biological activity in peanut pulp. The content of Ara h 1 peanut-sensitizing protein was reduced by 74.65% after fermentation. The protein extracted from fermented peanut pulp is more readily digestible by gastrointestinal juices. The inhibitory activity assay of hyaluronidase (an enzyme with strong correlation to allergy) increased from 46.65% to a maximum of 90.57% to reveal that LAB fermentation of peanut pulp exhibited a robust anti-allergic response. CONCLUSION: The strains identified in this study exhibited the ability to mitigate peanut allergenicity partially and to possess potential anti-allergic properties. Lactobacillus plantarum P1 and Lactobacillus salivarius C24 were identified as the most promising strains and were selected for further research. © 2023 Society of Chemical Industry.

Bioactivity-Guided Fraction from Viscera of Abalone, Haliotis discus hannai Suppresses Cellular Basophils Activation and Anaphylaxis in Mice.

Basophils and mast cells are specialized effector cells in allergic reactions. Haliotis discus hannai (abalone), is valuable seafood. Abalone male viscera, which has a brownish color and has not been previously reported to show anti-allergic activities, was extracted with acetone. Six different acetone/hexane fractions (0, 10, 20, 30, 40, and 100%) were obtained using a silica column via ß-hexosaminidase release inhibitory activity-guided selection in phorbol myristate acetate and a calcium ionophore, A23187 (PMACI)-induced human basophils, KU812F cells. The 40% acetone/hexane fraction (A40) exhibited the strongest inhibition of PMACI-induced-ß-hexosaminidase release. This fraction dose-dependently inhibited reactive oxygen species (ROS) production and calcium mobilization without cytotoxicity. Western blot analysis revealed that A40 down-regulated PMACI-induced MAPK (ERK 1/2, p-38, and JNK) phosphorylation, and the NF-κB translocation from the cytosol to membrane. Moreover, A40 inhibited PMACI-induced interleukin (IL)-1ß, IL-6, and IL-8 production. Anti-allergic activities of A40 were confirmed based on inhibitory effects on IL-4 and tumor necrosis factor alpha (TNF-α) production in compound (com) 48/80-induced rat basophilic leukemia (RBL)-2H3 cells. A40 inhibited ß-hexosaminidase release and cytokine production such as IL-4 and TNF-α produced by com 48/80-stimulated RBL-2H3 cells. Furthermore, it's fraction attenuated the IgE/DNP-induced passive cutaneous anaphylaxis (PCA) reaction in the ears of BALB/c mice. Our results suggest that abalone contains the active fraction, A40 is a potent therapeutic and functional material to treat allergic diseases.

Screening of Prospective Antiallergic Compound as FcεRI Inhibitors and Its Antiallergic Efficacy Through Immunoinformatics Approaches.

The occurrence of allergy, a type I hypersensitivity reaction, is rising exponentially all over the world. Sometimes, allergy proves to be fatal for atopic patients, due to the occurrence of anaphylaxis. This study is aimed to find an anti-allergic agent that can inhibit the binding of IgE to Human High Affinity IgE Receptor (FCεRI), thereby preventing the degranulation of mast cells. A considerable number of potential anti-allergic compounds were assessed for their inhibitory strength through ADMET studies. AUTODOCK was used for estimating the binding energy between anti-allergic compounds and FCεRI, along with the interacting amino acids. The docked pose showing favorable binding energy was subjected to molecular dynamics simulation study. Marrubiin, a diterpenoid lactone from Lamiaceae, and epicatechin-3-gallate appears to be effective in blocking the Human High Affinity IgE Receptor (FCεRI). This in-silico study proposes the use of marrubiin and epicatechin-3-gallate, in the downregulation of allergic responses. Due to the better inhibition constant, future direction of this study is to analyze the safety and efficacy of marrubiin in anti-allergic activities through in-vivo clinical human trials.

Epinastine Cream: A Novel Once-Daily Therapeutic Agent for Allergic Conjunctivitis.

Purpose: To investigate the in vivo efficacy of epinastine cream in type I allergic models. Methods: The dose, timing, and antiallergic effect of epinastine cream on the conjunctiva were evaluated postapplication to the eyelid skin of guinea pigs with histamine- or ovalbumin-induced allergic conjunctivitis. Additionally, we assessed its antiallergic effects on the skin postapplication to the dorsal skin of guinea pigs with ovalbumin-induced passive cutaneous anaphylaxis. Efficacy was estimated by determining the amount of dye that leaked from conjunctival or dorsal skin tissue vessels as a measure of vascular permeability, scoring the severity of allergic symptoms, and observing the scratching behaviors using clinical parameters. Results: In the histamine-induced conjunctivitis model, epinastine cream strongly inhibited conjunctival vascular permeability in a dose-dependent manner. The inhibitory effect of 0.5% epinastine cream 24 h postapplication was significantly higher than that of 0.1% epinastine hydrochloride ophthalmic solution 8 h postadministration. Additionally, the 0.5% epinastine cream inhibited conjunctival vascular permeability 15 min postapplication, and the effect was sustained over 24 h. Furthermore, the 0.5% epinastine cream effectively suppressed clinical symptom scores and exhibited ameliorated scratching bouts in conjunctival allergic reactions in the experimental allergic conjunctivitis model. Additionally, it significantly inhibited vascular permeability in skin allergic reactions in the passive cutaneous anaphylaxis model. Conclusions: The results suggest that epinastine cream is a strong, long-lasting, and skin-penetrating inhibitor of type I allergic reactions. The 0.5% epinastine cream applied once daily could be a promising, potent, and long-acting therapeutic agent for allergic conjunctivitis.

Dietary Polyphenols-Natural Bioactive Compounds with Potential for Preventing and Treating Some Allergic Conditions.

In light of the constantly increasing prevalence of allergic diseases, changes in dietary patterns have been suggested as a plausible environmental explanation for the development and progression of these diseases. Nowadays, much attention has been paid to the development of dietary interventions using natural substances with anti-allergy activities. In this respect, dietary polyphenols have been studied extensively as one of the most prominent natural bioactive compounds with well-documented anti-inflammatory, antioxidant, and immunomodulatory properties. This review aims to discuss the mechanisms underlying the potential anti-allergic actions of polyphenols related to their ability to reduce protein allergenicity, regulate immune response, and gut microbiome modification; however, these issues need to be elucidated in detail. This paper reviews the current evidence from experimental and clinical studies confirming that various polyphenols such as quercetin, curcumin, resveratrol, catechins, and many others could attenuate allergic inflammation, alleviate the symptoms of food allergy, asthma, and allergic rhinitis, and prevent the development of allergic immune response. Conclusively, dietary polyphenols are endowed with great anti-allergic potential and therefore could be used either for preventive approaches or therapeutic interventions in relation to allergic diseases. Limitations in studying and widespread use of polyphenols as well as future research directions are also discussed.

Recent Advancement and Novel Application of Natural Polyphenols for the Treatment of Allergy Asthma: From Phytochemistry to Biological Implications.

Allergic diseases, primarily IgE-mediated, exert a substantial global health burden. A pivotal role in allergic reactions is played by mast cells, with histamine serving as a central mediator. Within this context, plant-based polyphenols, abundantly present in vegetables and fruits, show promising potential for allergy prevention. These natural compounds, particularly flavonoids, possess anti-inflammatory and anti-allergic properties, influencing dendritic cells, modulating macrophages, and fostering the proliferation of B cells and T cells. The potent anti-allergic effects of flavonoids are attributed to their ability to reduce the production of signaling factors, suppress cytokine production, and regulate signal transduction and gene expression in mast cells, basophils, and T cells. Notably, their benefits extend beyond allergy prevention, as they hold promise in the prevention and treatment of autoimmune illnesses such as diabetes, rheumatoid arthritis, and multiple sclerosis. In the context of allergic reactions and autoimmune diseases, polyphenols exhibit immunomodulatory effects by inhibiting autoimmune T cell proliferation and downregulating pro-inflammatory cytokines. In recent times, flavonoids, being the most prevalent polyphenols in food, have garnered significant attention from researchers due to their potential health advantages. This review compiles the latest scientific research to highlight the impact of flavonoids on allergic illnesses and their potential as a beneficial dietary component.

The anti-allergic potential of stingless bee honey from different botanical sources via modulation of mast cell degranulation.

BACKGROUND: Allergy is an inflammatory disorder affecting around 20% of the global population. The adverse effects of current conventional treatments give rise to the increased popularity of using natural food products as complementary and alternative medicine against allergic diseases. Stingless bee honey, commonly known as Kelulut honey (KH) in Malaysia, has been used locally as a traditional remedy to relieve cough and asthma. This study evaluated the anti-allergic potential of KH collected from four different botanical sources on phorbol ester 12-myristate-3-acetate and calcium ionophore-activated human mast cells. METHODS: The present study examined the inhibitory effects of all collected honey on the release of selected inflammatory mediators, such as tumor necrosis factor-α (TNF-α), interleukin (IL)-4, IL-6, IL-8, histamine, and ß-hexosaminidase in an activated HMC. Besides that, all honey's total phenolic content (TPC) was also examined, followed by using liquid chromatography with tandem mass spectrometry (LC-MS/MS) to identify the phytochemicals in the honey. Further examination of the identified phytochemicals on their potential interaction with selected signaling molecules in an activated mast cell was conducted using computational methods. RESULTS: The results indicated that there were significant inhibitory effects on all selected inflammatory mediators' release by KH sourced from bamboo (BH) and rubber tree (RH) at 0.5% and 1%, but not KH sourced from mango (AH) and noni (EH). BH and RH were found to have higher TPC values and were rich in their phytochemical profiles based on the LC-MS/MS results. Computational studies were employed to determine the possible molecular target of KH through molecular docking using HADDOCK and PRODIGY web servers. CONCLUSIONS: In short, the results indicated that KH possesses anti-allergic effects towards an activated HMC, possibly by targeting downstream MAPKs. However, their anti-allergic effects may vary according to their botanical sources. Nevertheless, the present study has provided insight into the potential application of stingless bee honey as a complementary and alternative medicine to treat various allergic diseases.

PI3K/mTOR Inhibitor Dactolisib Attenuates Allergic Response Through Inhibitions of the Sensitization and Mast Cell Activation.

The aim of this study was to evaluate the anti-allergic potentials of dactolisib, a dual PI3K/mTOR kinase inhibitor, on two important events for allergy: sensitization and the onset of anaphylactic symptoms. After sensitization with the antigen ovalbumin (OVA), five successive oral administrations of dactolisib effectively decreased serum anti-OVA antibody-an indicator of sensitization-levels in mice. In parallel with the antibody levels in their serum, anaphylactic rectal temperature decrease induced by the re-administration of OVA to dactolisib-treated mice was strongly diminished compared to that in vehicle-treated mice. The inhibitor also inhibited ex vivo splenic B cell activation indicated by the increase of phosphorylation of Akt, CD69 expression levels, and proliferation upon anti-B cell receptor antibody treatment, suggesting that suppressive effects of the inhibitor on B cell activation plays a role in its ability to decrease sensitization in vivo. We concurrently observed the anti-anaphylactic ability of dactolisib in vivoand in vitro. A single oral administration of the inhibitor attenuated the anaphylactic rectal temperature decrease induced in a mouse model of passive systemic anaphylaxis. In in vitro mast cell models, pretreatment with the drug inhibited the degranulation response and cytokine production in RBL2H3 cells triggered by IgE and antigens, without affecting cell viability. These results suggest that dactolisib, as well as other PI3K/mTOR inhibitors, might be a good candidate for anti-allergic drugs that exhibit both anti-sensitizing and anti-anaphylactic effects.