Anti-allergic Effects Research Articles

Antimicrobial Peptide Pro10-1D Exhibits Anti-Allergic Activity: A Promising Therapeutic Candidate

Although antimicrobial peptides (AMPs) exhibit a range of biological functions, reports on AMPs with therapeutic effects in allergic disorders are limited. In this study, we investigated the anti-allergic effects of Pro10-1D, a 10-meric AMP derived from insect defensin protaetiamycine. Our findings demonstrate that Pro10-1D effectively inhibits antigen-induced degranulation of mast cells (MCs) with IC50 values of approximately 11.6 μM for RBL-2H3 cells and 2.7 μM for bone marrow-derived MCs. Furthermore, Pro10-1D suppressed the secretion of cytokines with IC50 values of approximately 2.8 μM for IL-4 and approximately 8.6 μM for TNF-α. Mechanistically, Pro10-1D inhibited the Syk-LAT-PLCγ1 signaling pathway in MCs and decreased the activation of mitogen-activated protein kinases (MAPKs). Pro10-1D demonstrated a dose-dependent reduction in IgE-mediated passive cutaneous anaphylaxis in mice with an ED50 value of approximately 7.6 mg/kg. Further investigation revealed that Pro10-1D significantly reduced the activity of key kinases Fyn and Lyn, which are critical in the initial phase of the FcεRI-mediated signaling pathway, with IC50 values of approximately 22.6 μM for Fyn and approximately 1.5 μM for Lyn. Collectively, these findings suggest that Pro10-1D represents a novel therapeutic candidate for the treatment of IgE-mediated allergic disorders by targeting the Lyn/Fyn Src family kinases in MCs.

Comprehensive Analysis of Allerkhand Tablet: A Novel Ayurvedic Herbal Formulation helps to regulates the Allergic Conditions

The increasing interest in alternative and complementary therapies has spotlighted Ayurveda, an ancient system of medicine, for its holistic approach in managing allergies. Ayurvedic treatments for allergy typically focus on restoring balance of the Vitiated Doshas. This may involve dietary corrections, lifestyle changes, and the use of herbal remedies and rejuvenation therapies. Curcumin, the active component of turmeric, has been extensively studied for its anti-inflammatory, antioxidant, and immunomodulatory properties, which can be beneficial in managing allergic conditions. The current study was conducted for a scientific evaluation of Allerkhand tablet, an Ayurvedic patent medicine used to treat allergy and boost immunity. Allerkhand, a poly-herbal tablet formulation with Curcuma longa as the main ingredient and 18 other constituents, serves to improve immunity by combining anti-allergic and anti-histaminic effects. The product was subjected to qualitative phytochemical HPTLC, HPLC, and anti-microbial studies. Phytochemical analysis of Allerkhand in aqueous and methanolic extracts revealed the presence of 13 and 8 common compounds, respectively. According to HPTLC and HPLC analysis, sufficient quantity of curcuminoids are present in tablets. Significant antimicrobial zones were found against six bacterial strains. These findings support the traditional use of Allerkhand tablets as a natural remedy in regulating allergic conditions.

RESEARCH OF STEROID AND VOLATILE COMPOUNDS IN VERBENA OFFICINALIS L. HERB

Biologically active compounds of medicinal plants are able to affect various links of processes in the living organism, namely, they regulate the processes of metabolism, growth and development of organisms. The therapeutic potency of medicinal plant raw materials is derived by a complex of biologically active compounds that influence various biologically processes, including metabolism, growth, and development. Numerous steroid-like remedies of plant origin exhibit remarkable activity. Phytosterols, chemical compounds similar to cholesterol, are synthesized in plant organisms and have been found to have anti-tumor effects and lower blood cholesterol. Additionally, steroid and volatile compounds demonstrate antimicrobial and anti-inflammatory activity. The genus Verbena includes 250 species. 3 species grow on the territory of Ukraine: Verbena officinalis L., Verbena supinа L., Verbena hybrida Hort. Verbena officinalis L. is globally recognized for its antioxidant and antimicrobial properties, showcasing anti-inflammatory, antiseptic, antispasmodic, and anti-allergic effects. However, comprehensive chemical studies of Verbena officinalis L. are limited, necessitating a detailed analysis of phitosterol and volatile compound content using modern precise methods. The aim of the research was to qualitatively and quantitatively determine the content of steroid and volatile compounds in Verbena officinalis L. herb using gas chromatography/mass spectrometry. We chose the herb Verbena officinalis L. as the object of the study. Materials and methods. The content of phytosterols and volatile compounds in Verbena officinalis L. herb was studied using the GC/MS method. We chose the herb Verbena officinalis L. as the object of the study. An Agilent Technologies 6890 chromatograph with a 5973 mass spectrometric detector with an HP-5 ms capillary column were used. The mass spectra library in conjunction with AMDIS and NIST identification programs was employed for components were identification. Research results. The study of phytosterols in Verbena officinalis L. identified campesterol (9.32%), stigmasterol (7.13%), γ-sitosterol (72.21%) and androst-5,15-dien-3-ol-acetate were identified (11.35%). In the volatile fraction 8 compounds were identified, with benzophenone (33.96%) and hexahydro farnesyl acetone (22.57%) being dominant. Conclusions. The GC/MS method allowed for the qualitative and quantitative analysis of steroid and volatile compounds in Verbena officinalis L, identifying 4 phytosterols and 8 volatile compounds. The identified phytosterols and volatile compounds in the herb have significant implications for the production of phytoremedies and the development of raw material standardization parameters. We identified campesterol, stigmasterol, γ-sitosterol and androst-5,15-dien-3-ol-acetate in the herb Verbena officinalis L. Eight volatile compounds were identified in the herb Verbena officinalis L. by the chromato-mass spectrometric method. Benzophenone and hexahydro farnesyl acetone are dominant. Steroid compounds (mg/kg) were identified and quantified: campesterol, stigmasterol, γ-sitosterol and androst-5,15-dien-3-ol-acetate. The obtained research results will be taken into account in the further production of phytoremedies based on the medicinal Verbena herb, as well as in the development of raw material standardization parameters.

An Experimental Mice Model for Ovalbumin‐Induced Allergic Rhinitis Imbued With Copper Oxide Green Nanoparticles From Leaf Extract of Laurus nobilis

ABSTRACTThis study aims to develop a safer and more effective treatment for allergic rhinitis using green‐synthesized copper oxide nanoparticles (CuO NPs) derived from Laurus nobilis (L. nobilis), addressing the limitations of current therapies. The environmentally friendly CuO NPs were evaluated for their antiallergic, anti‐inflammatory, and antimicrobial properties. Various analytical techniques confirmed the successful synthesis of CuO NPs. Phytoconstituents were identified using GC–MS, and molecular docking studies indicated that eugenol and 1H‐cyclopropazulen‐7‐ol, present in L. nobilis leaf extract, could be potential therapeutics targeting the FGFR2 protein. The antibacterial activity of CuO NPs was significant against Gram‐positive (Bacillus subtilis [B. subtilis] and Staphylococcus aureus [S. aureus]) and Gram‐negative (Escherichia coli [E. coli] and Klebsiella pneumoniae [K. pneumoniae]) bacterial strains. In a mouse model, the antiallergic effects were demonstrated by a significant reduction in symptoms like rubbing and sneezing and a decrease in inflammatory cell counts and mediators, including neutrophils, eosinophils, macrophages, lymphocytes, RORc, IL‐17A, IL‐5, IL‐13, and IL‐6. The preclinical results suggest that CuO NPs possess promising antibacterial, antiallergenic, and anti‐inflammatory properties.

Cordyceps militaris Grown on Germinated Rhynchosia nulubilis (GRC) Encapsulated in Chitosan Nanoparticle (GCN) Suppresses Particulate Matter (PM)-Induced Lung Inflammation in Mice.

Cordyceps militaris grown on germinated Rhynchosia nulubilis (GRC) exerts various biological effects, including anti-allergic, anti-inflammatory, and immune-regulatory effects. In this study, we investigated the anti-inflammatory effects of GRC encapsulated in chitosan nanoparticles (CN) against particulate matter (PM)-induced lung inflammation. Optimal CN (CN6) (CHI: TPP w/w ratio of 4:1; TPP pH 2) exhibited a zeta potential of +22.77 mV, suitable for GRC encapsulation. At different GRC concentrations, higher levels (60 and 120 mg/mL) led to increased negative zeta potential, enhancing stability. The optimal GRC concentration for maximum entrapment (31.4 ± 1.35%) and loading efficiency (7.6 ± 0.33%) of GRC encapsulated in CN (GCN) was 8 mg/mL with a diameter of 146.1 ± 54 nm and zeta potential of +30.68. In vivo studies revealed that administering 300 mg/kg of GCN significantly decreased the infiltration of macrophages and T cells in the lung tissues of PM-treated mice, as shown by immunohistochemical analysis of CD4 and F4/80 markers. Additionally, GCN ameliorated PM-induced lung tissue damage, inflammatory cell infiltration, and alveolar septal hypertrophy. GCN also decreased total cells and neutrophils, showing notable anti-inflammatory effects in the bronchoalveolar lavage fluid (BALF) from PM-exposed mice, compared to GRC. Next the anti-inflammatory properties of GCN were further explored in PM- and LPS-exposed RAW264.7 cells; it significantly reduced PM- and LPS-induced cell death, NO production, and levels of inflammatory cytokine mRNAs (IL-1β, IL-6, and COX-2). GCN also suppressed NF-κB/MAPK signaling pathways by reducing levels of p-NF-κB, p-ERK, and p-c-Jun proteins, indicating its potential in managing PM-related inflammatory lung disease. Furthermore, GCN significantly reduced PM- and LPS-induced ROS production. The enhanced bioavailability of GRC components was demonstrated by an increase in fluorescence intensity in the intestinal absorption study using FITC-GCN. Our data indicated that GCN exhibited enhanced bioavailability and potent anti-inflammatory and antioxidant effects in cells and in vivo, making it a promising candidate for mitigating PM-induced lung inflammation and oxidative stress.

Unveiling Potent Anti-Asthmatic Effect of Curcumin in Combination with Salmeterol in Swiss Albino Mice

Background: Asthma is a long-term inflammatory respiratory condition marked by alterations in the airways and an increase in inflammatory cell infiltration. It has been observed that Curcumin possesses immune-modulating, anti-inflammatory, and relaxing properties for smooth muscle in the airways. Salmeterol is believed to ease the smooth muscles of the airways. Objective: Swiss Albino mice were used in the research to examine the combination anti-asthmatic effects of Curcumin and Salmeterol in asthma produced by ova albumin and milk induced eosinophilia and leucocytosis. Methods: The mice received pre-treatment with Curcumin (10 mg/kg, 20 mg/kg intraperitoneally) as well as Salmeterol (5 mg/kg) after being stimulated with an Ovalbumin (OVA) challenge and milk. After the induction period, various hematological, biochemical, molecular (ELISA), and histological analyses were performed. Results: The findings demonstrated that the combined treatment decreased the animal’s overall leukocyte and eosinophil numbers in a manner that was dose-dependent. Additionally, the therapy reduced albumin and overall protein amount in serum, BALF and lung tissues, facilitated changes in haematological parameters, and reduced the rise of Th2 cytokines (IL-4, TNF-α, IL-13) levels that is induced by OVA in lungs and BALF, total IgE level in serum. The combined action of Curcumin and Salmeterol reduced OVA-induced inflammatory influx and ultrastructural abnormalities, according to histopathological evaluation. Conclusion: The findings of this investigation demonstrate that curcumin and salmeterol together possess anti-asthmatic effects through suppressing Th2 triggered immune response and possessing an anti-inflammatory effect and anti-allergic effect. Thus combination of treatments might be a novel technique for managing asthma.

Volvariella volvacea (paddy straw mushroom): A mushroom with exceptional medicinal and nutritional properties

Volvariella volvacea, commonly referred to as paddy straw mushroom, is renowned for its remarkable medicinal and nutritional properties. This mushroom, part of the family Pluteaceae, thrives in tropical and subtropical regions and is highly esteemed for its distinctive flavor and substantial health benefits. The fruiting body of V. volvacea is a rich source of bioactive compounds, including antioxidant enzymes, terpenes, polypeptides, sugars, phenolics, and flavonoids. These compounds exhibit an extensive range of therapeutic activities such as anti-tumor, anti-microbial, antioxidant, anti-malarial, anti-cancer, anti-inflammatory, and anti-allergic effects. Nutritionally, V. volvacea is an excellent source of carbohydrates, proteins, fibers, ascorbic acid, and essential minerals. It also boasts a comprehensive profile of amino acids, including valine, arginine, glutamine, serine, aspartic acid, leucine, isoleucine, tyrosine, asparagine, lysine, cystine, proline, glycine, tryptophan, methionine, phenylalanine, threonine, and histidine. This review emphasizes the significant medicinal and nutritional potential of V. volvacea, advocating its inclusion as a functional food to enhance human health and well-being. By highlighting its diverse bioactive compounds and therapeutic benefits, this review aims to foster greater recognition and utilization of paddy straw mushroom in both dietary and medicinal applications.

An Overview of Apple Varieties and the Importance of Apple Consumption in the Prevention of Non-Communicable Diseases—A Narrative Review

Non-communicable diseases such as cardiovascular diseases, cancers, diabetes, and asthma are increasingly common due to factors like industrialization, urbanization, fast-paced life, stress, sedentary lifestyle, and unbalanced diet in the 21st century. These chronic conditions are a global epidemic, being among the top causes of death worldwide. Preventing these diseases through a nutritious diet is crucial, and scientific studies suggest that appropriate fruit intake, particularly apples, can lower the risk of various health issues. Apples, rich in bioactive compounds, vitamins, minerals, and dietary fiber, offer numerous health benefits. Regular consumption of apples helps reduce the risk of atherosclerosis, coronary artery disease, heart attacks, and diabetes, and also provides anti-asthmatic and anti-allergic effects. Apples aid in detoxification, improve digestion, enhance skin, hair, and nail health, and offer protection against cancers, Alzheimer’s, and Parkinson’s disease. Apples have been a dietary staple for centuries, consumed in various forms like juices, sauces, and ciders. The reviewed article emphasizes the health benefits of apples, highlighting their role in preventing civilization diseases. It also discusses the characteristics of common apple varieties and the impact of thermal processing on their nutritional content.

4-hydroxyderricin from Angelica keiskei: Analysis, Preparation, and Multiple Skin Care Effects

Introduction: The content of the bioactive component 4-hydroxyderricin (4-HD) in the roots, stems, and leaves of Angelica keiskei (Umbelliferae), a well-known medicinal and edible plant, was analyzed by HPLC. The dry root contained the highest level (2. 69 ± 0.09 mg/g) of 4-HD, which was then prepared and spectroscopically identified by column chromatography. Method: The multiple skin care activities of 4-HD, including skin whitening, anti-allergy, and anti-inflammation, were evaluated on enzymatic and cellular models. 4-HD showed a significant inhibitory effect on mushroom tyrosinase, and it could also strongly suppress the activity of tyrosinase in B16F10 cells. A molecular docking study revealed that 4-HD could closely bind to tyrosinase through hydrogen bonding and hydrophobic interactions. Results: In the anti-allergic assay, 4-HD could effectively reduce the degranulation rate in the neutral red staining test and largely down-regulate the release level of β-HEX in RBL-2H3 cells at the concentration of 5 μM. 4-HD decreased the production of NO in RAW264.7 cells induced by Lipopolysaccharide (LPS), showing its anti-inflammatory effect. Conclusion: The skin whitening, anti-allergic, and anti-inflammatory effects of 4-HD have clearly demonstrated its potential usage in the pharmaceutical and cosmetic industries.

Propolis in Human Health: Unraveling Chemistry, Applications, and Efficacy

The paper explores the diverse aspects of propolis, a resinous substance created by bees from botanical sources, presenting a comprehensive overview of its chemistry, applications, and efficacy in human health. Propolis, colloquially known as "bee glue," serves as a versatile material in hive construction and defense against diseases and predators. Its chemical composition, influenced by geographic origins, comprises a myriad of bioactive compounds, including flavonoids, phenolic acids, terpenoids, and more. The study delves into the pharmacological activities of propolis, emphasizing its antioxidant, antimicrobial, anti-inflammatory, and anticancer properties. Propolis exhibits a direct correlation between its biological activity and the quality of its chemical constituents. The antioxidant activity, attributed to flavonoids, plays a crucial role in mitigating oxidative stress and associated chronic inflammation. Furthermore, the paper discusses the therapeutic potential of propolis in various health conditions, such as diabetes mellitus, cardiovascular diseases, asthma, COPD, and wound healing. In diabetes, propolis shows promise in reducing blood glucose levels and insulin resistance. Its cardioprotective effects are linked to antioxidant compounds, addressing oxidative stress in cardiovascular diseases. Propolis demonstrates anti-allergic and anti-inflammatory effects in respiratory conditions, providing potential relief for asthma and COPD patients. Additionally, propolis accelerates wound healing through its immunomodulatory, antimicrobial, and antioxidant properties. In conclusion, propolis emerges as a natural resource with significant potential for human health, presenting a diverse array of bioactive compounds that contribute to its therapeutic efficacy across various medical conditions. The multifaceted nature of propolis makes it a subject of growing interest for further research and exploration in the field of medicine and healthcare.

Phytochemical analysis of the methanolic extract from the mangrove species Avicennia marina plant species inhabited in coastal water

The mangrove, a vital ecosystem, faces significant threats from climate change, human actions, and pollution. This study aims to evaluate the presence and distribution of trace metals (Cu, Cd, Ni, Pb, and Zn) in Avicennia marina leaves and sediments, shedding light on A. marina’s antioxidant capabilities amidst metal pollution. Samples were gathered from Pichavaram coastal areas. Various pollution indices such as contamination factor (CF), pollution load index (PLI), and bio concentration factor (BCF) were utilised to gauge pollution levels. Analysis via LC/MS,1H & 13C-NMR, and GC/MS revealed 52 compounds in the methanolic extract of A. marina notably; the extract contains pentanoic acid, decanoic acid, diethyl hydroxylamine, pyrrolidine, 4-chlorophenyl, octadecylisocyanate, thiazolidinones, and arabinopyranoside. These compounds exhibit diverse biological properties, such as antioxidative, anticancer, antimicrobial, anti-inflammatory, antiallergic, antiaging, and antiartherosclerotic effects, making them promising herbal medicines with minimal adverse effects and maximum efficacy, thereby improving the quality of life during treatment.

Antibacterial and Antiallergic Effects of Three Tea Extracts on Histamine-Induced Dermatitis.

Atopic dermatitis (AD) is a persistent and recurrent inflammatory skin condition with a genetic basis. However, the fundamental reasons and mechanisms behind this phenomenon remain incompletely understood. While tea extracts are known to reduce histamine-induced skin allergies and inflammation, the specific mechanisms by which various types of Chinese tea provide their protective effects are still not fully elucidated. In this study, a model of skin itching induced by histamine is used to explore the functions and mechanisms of three types of tea extract (Keemun black tea (HC), Hangzhou green tea (LC), and Fujian white tea (BC)) in alleviating histamine-induced dermatitis. The components of three tea extracts are identified by UPLC-Q-TOF-MS, and we found that their main components are alkaloids, fatty acyls, flavonoids, organic acids, and phenols. The inhibitory effects of three types of tea extract on Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) in skin injury are investigated by MIC and flow cytometry. The three types of tea extract have an inhibitory effect on the growth of bacterial flora, with HC showing the best inhibitory activity. The effect of the three types of tea extract on histamine-induced dermatitis is also evaluated. Furthermore, itchy skin experiments, HE staining, toluidine blue staining, and immunohistochemical staining of mouse skin tissues were performed to determine the variations of scratching, epidermal thickness, mast cell number, IL-1β, and NGF content after the administration of the tea extracts. The three types of tea extracts all alleviate and inhibit skin itching, epidermal hyperplasia, and allergic dermatitis. BC effectively alleviates epidermal hyperplasia caused by skin allergies, and LC significantly downregulates NGF. HC reduces histamine-induced mast cell infiltration and downregulates IL-1β to alleviate skin itching. Consequently, tea emerges a potent natural product that can inhibit the growth of skin wound bacterial flora and exhibit skin repair effects on histamine-induced allergic dermatitis.

Guaijaverin And Epigallocatechin Gallate Exerts Antiinflammatory And Antiallergenic Effects Through Interleukin-12 Production.

Our aim in the current study was to determine the in vitro and invivo synergistic antiinflammatory and antiallergic effect associated with the IL-12 production of guaijaverin and epigallocatechin gallate (EGCG) complex (GEC) and ILS-F-2301 (2:8 extract of Psidium guajava and Camellia sinensis). Compared to EGCG alone, GEC showed synergistic inhibition of nitric oxide (NO), inducible NO synthase, and cyclooxygenase-2 by 3.8, 5.1, and 4.1%, respectively. The downregulation of interleukin-12 (IL-12) by 2,4-dinitrophenyl-human serum albumin conjugate/DNP-immunoglobulin E or ovalbumin (OVA) was synergistically increased by GEC by about 7.5% or 5.4% compared to EGCG alone. The level of downregulation of IL-12 in plasma increased by 100 mg/kg with ILS-F-2301 (28.7%) when compared to the OVA/Alu-treated group. Also, GEC synergistically increased by GEC by about 7.5% or 5.4% compared to EGCG alone. The level of down and cyclooxygenase C synergistically inhibited p-Akt, PI3K, mTOR, p-STAT6, and GATA3 by 4.9%, 4.1%, 19.2%, 23.8%, and 35.3%, respectively, while increasing the expressions of p-STAT1 and T-bet (showing 53.3% and 9.4% activation) when compared to EGCG alone. In an allergenic rhinitis mouse model, 100 mg/kg of ILS-F-2301 was shown to inhibit p-Akt, PI3K, mTOR, p-c-Jun N-terminal kinase (p-JNK), p-extracellular signal-regulated kinase (p-ERK), and p-p38 by 23.3%, 43.8%, 17.2%, 32.2%, 29.1%, and 41.8% when compared to the OVA/Alu-sensitized group. Taken together, our findings suggest that ILS-F-2301 may have potential as a functional food for alleviating antiallergic rhinitis.

Guaijaverin and Epigallocatechin Gallate Complex Modulate Th1 and Th2 Cytokine-Mediated Allergic Responses Through STAT1/T-bet and STAT6/GATA3 Pathways.

We aimed to determine the in vitro and invivo synergistic antiallergic effect of guaijaverin and epigallocatechin gallate (EGCG) complex (GEC), and the antiallergic rhinitis (AR) properties of guaijaverin-rich Psidium guajava and EGCG-rich Camellia sinensis (ILS-F-2301). GEC showed synergistic inhibition of β-hexosaminidase by 4.20% and interleukin (IL)-4, -5, and -13 by 4.08%, 0.67%, and 4.71%, respectively, while increasing interferon (IFN)-γ by 12.43%, compared with EGCG only. In addition, 50 μg/mL of ILS-F-2301 inhibited β-hexosaminidase release, and inhibited IL-4, -5, and -13 by 61.54%, 58.79%, and 59.25%, respectively, while increasing IFN-γ (showing 133.14% activation). Moreover, 50 μg/mL of ILS-F-2301 suppressed p-STAT6 and GATA3, while p-STAT1 and T-bet increased, and 0.039 μg/mL of guaijaverin or 5.275 μg/mL of EGCG modulated T helper (Th)1- and Th2-related proteins. These data suggested that guaijaverin and EGCG in ILS-F-2301 was the main active compound involved in Th1/Th2 modulation. In the AR mouse model, the administration of ILS-F-2301 inhibited ovalbumin (OVA)-specific IgE, histamine in serum; it also inhibited IL-4 and -5 by 28.23% and 47.15%, respectively, while increasing IFN-γ (showing 37.11% activation), compared with OVA/Alu-treated mice. Taken together, our findings suggest that ILS-F-2301 is a functional food for alleviating anti-AR.

Indirubin induces tolerogenic dendritic cells via aryl hydrocarbon receptor activation and ameliorates allergic asthma in a murine model by expanding Foxp3-expressing regulatory T cells

BackgroundAllergic asthma is a chronic bronchial inflammatory disease closely associated with abnormal immune responses of dendritic cells (DCs) and allergen-specific type 2 T helper (Th2) cells. Indirubin (IR), a natural aryl hydrocarbon receptor (AhR) ligand, exerts anti-inflammatory and immunomodulatory properties. PurposeIn this study, we aimed to clarify whether IR exhibits immunomodulatory action on DCs via AhR activation and investigated the antiallergic effects of IR in a mouse model of allergic asthma. MethodsLipopolysaccharide (LPS)-activated bone marrow-derived DCs were treated with IR. Their mRNA expressions, cytokine production, and phenotype patterns were determined by a quantitative real-time PCR, ELISA, flow cytometry, and RNA sequencing. The mixed lymphocyte reaction was utilized to evaluate the regulatory function of IR-treated DCs on T-cell differentiation. Moreover, mice with ovalbumin (OVA)-induced allergic asthma were treated with IR. Thereafter, the airway hyperresponsiveness (AHR), allergen-specific IgE production, cytokine levels, airway inflammation, and T-cell responses were evaluated. ResultsTreatment of LPS-stimulated DCs with 20 μM IR significantly reduced IL-12 and TNF-α production while increasing IL-10 secretion. Meanwhile, these DCs expressed decreased levels of CD80 but increased levels of Jagged 1 surface molecules. However, the effects of IR on DCs were reversed by pretreatment with the AhR antagonist, CH223191. Additionally, the coculture of these tolerogenic-like DCs with allogeneic CD4+T cells promoted the generation of Foxp3+ regulatory T (Treg) cells. A transcriptomic analysis identified several downregulated genes that are involved in regulating cell migration, cytokine secretion, and inflammatory responses in DCs after IR treatment. In an asthmatic murine model, oral administration of 25 mg kg-1 body weight of IR efficiently alleviated the development of AHR, OVA-specific IgE production, and levels of Th2-type cytokines (IL-4, IL-5, and IL-13) and the CCL11 chemokine. IR treatment also attenuated inflammatory cell recruitment and mucus production in the lungs. Notably, an enhanced frequency of Foxp3+ Treg cells and reduced effector T-cell proliferation associated with increased levels of IL-10 and TGF-β were observed in IR-treated mice. ConclusionIR can induce tolerogenic-like BMDCs which promote the differentiation of Treg cells. Importantly, the expansion of Foxp3+ Treg cells contributed to the therapeutic efficacy of IR against allergic asthma.

Anti-Allergic and Anti-Inflammatory Effects of Lidocaine-Derived Organic Compounds in a House Dust Mite-Induced Allergic Rhinitis Mouse Model.

Allergic rhinitis (AR) is a common chronic disease that significantly impacts the quality of life. Lidocaine is known to have anti-inflammatory and immunomodulatory effects. This study evaluated the effect of lidocaine analogs in a Dermatophagoides pteronyssinus (DP)-induced AR mouse model. An AR model was developed using BALB/c mice via intraperitoneal sensitization with DP and intranasal challenge with DP. One hour before stimulation with DP, lidocaine analogs, EI137 and EI341 (at a dose of 0.5 or 5 ug/g), were administered intranasally. Nasal symptoms and serum total IgE, interleukin (IL)-4, IL-10, interferon (IFN)-γ, and tumor necrosis factor (TNF)-α levels were evaluated. Reverse-transcription polymerase chain reaction was used to determine IL-4, IL-10, and IFN-γ, as well as the expression of their mRNA transcription factors in the sinonasal mucosa. Histologic changes were evaluated using hematoxylin and eosin and periodic acid-Schiff staining. The DP-induced AR mouse model had increased serum levels of total IgE and cytokines. EI137 and EI341 significantly suppressed the levels of total IgE, IL-4, and TNF-α. Intranasal instillation of EI137 and EI341 significantly inhibited IL-4, IL-10, and IFN-γ mRNA expression, as well as inflammatory cells and mucus-producing goblet cells. Lidocaine analogs also suppressed DP-stimulated IL-4, IFN-γ, and IFN-γ production by splenocytes. Intranasal instillation of EI137 and EI341 exhibited anti-allergic and anti-inflammatory effects, influenced by Th1 and Th2 inflammatory cytokines. These lidocaine analogs suppressed DP-induced sinonasal mucosal inflammation, inflammatory cell infiltration, and mucus hypersecretion.

Synthesis and PASS-assisted evaluation of new heterocyclic compounds containing hydroquinoline scaffolds

Currently, there is a growing interest in the synthesis of heterocyclic compounds containing hydroquinoline fragments. This surge can be attributed to the broad range of pharmaceutical and industrial applications that these compounds possess. In this study, the synthesis of both linear and fused heterocyclic systems that incorporate hydroquinoline fragments was described. Furthermore, the pharmacological activity spectra of the synthesized compounds were predicted using the in silico method, employing the Prediction of Activity Spectra of Substances (PASS) program. Hydroquinolines containing the nitrile functionality 7 and 8 were synthesized through the reaction of the corresponding hydroquinolinecarbaldehyde 5a, 6b with hydroxylamine hydrochloride and iodine in aqueous ammonia under ambient conditions, respectively. 2-Phenyl-1,3-oxazol-5(4 H)-ones 9a, b and 10a, b were synthesized via the condensation of compounds 5a, b and 6a, b with hippuric acid in acetic acid in 30–60% yield. When the methyl activated 7-methylazolopyrimidines 11a, b were reacted with N-alkyl-2,2,4-trimethyl-1,2,3,4-tetrahydroquinoline-6-carbaldehydes 6a, b, 60–70% yield of triazolo/pyrazolo[1,5-a]pyrimidin-6-yl carboxylic acids 12a, b were obtained. The condensation of 7-hydroxy-1,2,3,4-tetramethyl-1,2-dihydroquinoline 3 h with dimethylacetylenedicarboxylate (DMAD) and ethyl acetoacetate afforded cyclic products 16 and 17, respectively. The condensation reaction of 6-formyl-7-hydroxy-1,2,2,4-tetramethyl-1,2-dihydroquinoline 5e with methylene-active compounds such as ethyl cyanoacetate/dimethyl-3-oxopentanedioate/ethyl acetoacetate/diethylmalonate/Meldrum’s acid afforded 3-substituted coumarins 19 and 21 containing dihydroquinoline moiety. The pentacyclic coumarin 22 was obtained via the tandom condensation reaction of malononitrile with 5e in the presence of a catalytic amount of piperidine in ethanol. The biological activities of the synthesized compounds were predicted using the PASS program. Based on the prognosis, compounds 13a, b, and 14 exhibited a high likelihood of being active as inhibitors of gluconate 2-dehydrogenase, as well as possessing antiallergic, antiasthmatic, and antiarthritic properties, with a probability value (Pa) ranging from 0.849 to 0.870. Furthermore, it was discovered that compounds 7 and 8 tended to act as effective progesterone antagonists and displayed antiallergic, antiasthmatic, and antiarthritic effects (Pa = 0.276–0.827). Among the hydroquinolines containing coumarin moieties, compounds 17, 19a, and 19c were predicted to be potent progesterone antagonists, with Pa values of 0.710, 0.630, and 0.615, respectively.Graphical

Levilactobacillus brevis IBARAKI-TS3 Isolated From Pickles Promotes Production of Interleukin-10 via Toll-Like Receptor 2 in Human M2 Macrophages.

M2 macrophages play an important role in food allergy. Several studies have reported that lactic acid bacteria isolated from pickles exert antiallergic effects. We investigated the effects of several strains of lactic acid bacteria on the immune function of M2 macrophages. M2 macrophages differentiated from THP-1 cell line by interleukin-4 (IL-4) and IL-13 strongly expressed CD163, CD206, and HMOX1 mRNA. Levilactobacillus brevis IBARAKI-TS3 (IBARAKI-TS3) isolated from pickles was identified as a lactic acid bacterium that enhances the expressions of IL-10 and EBI3 mRNA in M2 macrophages. IBARAKI-TS3 induced the expression of genes involved in Toll-like receptor (TLR) signaling, such as IRAK, mitogen-activated protein kinases (MAPKs), and NF-κB mRNA. IBARAKI-TS3-induced IL-10 production was suppressed by anti-TLR2-neutralizing antibodies. Furthermore, the IBARAKI-TS3-induced increase in IL-10 levels was significantly reduced in TLR2-knockdown M2 macrophages compared to M2 macrophages. These results suggest that IBARAKI-TS3 promotes of IL-10 production via TLR2 in M2 macrophages.

Diterpenoid DGT alleviates atopic dermatitis–like responses in vitro and in vivo via targeting IL-4Rα

BackgroundAtopic dermatitis is a common chronic inflammatory skin disease characterized by relapsing eczema and intense itch. DGT is a novel synthetic heterocyclic diterpenoid derived from plants. Its therapeutic potential and mechanism(s) of action are poorly understood. ObjectivesWe investigated the potent therapeutic effect of DGT on atopic dermatitis, exploring the underlying mechanisms and determining whether DGT is a safe and well-tolerated topical treatment. MethodsWe observed anti-inflammatory effects of DGT on tumor necrosis factor-α/interferon-γ–treated human keratinocytes, and anti-allergic effects on immunoglobulin E–sensitized bone marrow–derived mast cells. In vivo, DGT was topically applied to two experimental mouse models of atopic dermatitis: oxazolone-induced sensitization and topically applied calcipotriol. Then the therapeutic effects of DGT were evaluated physiologically and morphologically. Moreover, we performed nonclinical toxicology and safety pharmacology research, including general toxicity, pharmacokinetics, and safety pharmacology on the cardiovascular, respiratory, and central nervous systems. ResultsIn keratinocytes, DGT reduced the expression of inflammatory factors, promoting the expression of barrier functional proteins and tight junctions and maintaining the steady state of barrier function. DGT also inhibited the activation and degranulation of mast cells induced by immunoglobulin E. Moreover, we found that interleukin-4 receptor-α was the possible target of DGT. Meanwhile, DGT had therapeutic effects on oxazolone/calcipotriol-treated mice. Notably, our pharmacology results demonstrated that DGT was safe and nontoxic in our studies. ConclusionDGT’s potent anti-inflammatory effects and good safety profile suggest that it is a potential candidate for the treatment of atopic dermatitis.

Aloe-emodin relieves allergic contact dermatitis pruritus by inhibiting mast cell degranulation

Urushiol-induced allergic contact dermatitis (ACD) is a chronic inflammatory skin disease in which skin barrier dysfunction leads to pruritus and eczematous lesions. ACD is triggered by immune imbalance. Aloe emodin is an anthraquinone derivative extracted from rhubarb, aloe and other traditional Chinese medicines. It has a wide range of pharmacological effects, including anti-inflammatory, anti-tumor, and anti-allergic effects. The purpose of our study was to demonstrate the effectiveness of aloe-emodin on urushiol-induced acute pruritus and allergic contact dermatitis. The results showed that urushiol could stimulate keratinocytes to release chemokines CXCL1, CXCL2, CCL2, TSLP, and TNF-α, which recruit or activate mast cells. Aloe-emodin treatment inhibited inflammatory-response-induced mast cell degranulation in skin lesions and suppressed the expression of inflammatory cytokines, such as interleukin-4, and interleukin-6. Therefore, the results indicate that aloe-emodin can improve urushiol-induced acute pruritus and allergic contact dermatitis in mice by inhibiting mast cell degranulation.