IgE receptor on the surface of mast cells with high affinity (3) and induces IgE‐dependent acute hypersensitivity reactions. Furthermore, crosslinking of antigen‐IgE triggers the IgE receptor‐mediated activation of mast cells and induces the degranulation of mast cells through granule membrane
نویسندگان
چکیده
Allergic inflammation is induced by allergens and leads to various allergic diseases, including rhinitis, asthma and conjunctivitis. Histamine is important in the pathogenesis of an immunoglobulin E‐dependent allergic reaction and results in the secretion of cytokines associated with inflammation. Angelica dahurica (A. dahurica) is a medicinal plant widely used in China for the treatment of symptoms related to allergic inflammation. The present study investigated the chemical constituents from A. dahurica and evaluated their reductive effect on allergic inflammation. As a result, 15 compounds including 13 coumarins have been identified as isoimperatorin (1), imperatorin (2), oxypeucedanin (3), oxypeucedanin hydrate (4), bergapten (5), byakangelicin (6), phellopterin (7), byakangelicol (8), isopimpinellin (9), xanthotoxol (10), xanthotoxin (11), pimpinellin (12), scopoletin (13), β‐sitosterol (14) and daucosterol (15). Compounds 1‐13 were able to reduce the release of histamine, with compounds 4‐6 exhibiting the most potent activity. Furthermore, compounds 1‐12 were able to inhibit the secretion of tumor necrosis factor‐α, interleukin (IL)‐1β and IL‐4, with compounds 5 and 7 exhibiting the strongest inhibitory effects. These compounds implemented the inhibitory effects on the expression of inflammatory cytokine genes through the inhibition of nuclear factor‐κB activation. Virtual screening by a docking program indicated that compound 3 is a potent histamine H1 receptor antagonist. Additionally, the calculated physicochemical properties of these compounds support most furanocoumarins to be delivered to binding sites and permeate the cell membrane. The present findings contribute to understanding how A. dahurica attenuates allergic inflammation. Introduction Allergic inflammation is caused by allergens and results in diseases, including rhinitis, asthma and conjunctivitis. It impacts the quality of life and costs large medical expenditures to attenuate the hypersensitive symptoms. In total, 10‐20% of the population worldwide suffers from allergies, and this number annually increases (1). Similarly to effector cells, mast cells are important in allergic inflammation through the production and secretion of allergic mediators, including histamine, chemokines, cytokines and growth factors (2). When exposed to allergens the stimulation leads to the production of immunoglobulin E (IgE) within min, which binds to the IgE receptor on the surface of mast cells with high affinity (3) and induces IgE‐dependent acute hypersensitivity reactions. Furthermore, crosslinking of antigen‐IgE triggers the IgE receptor‐mediated activation of mast cells and induces the degranulation of mast cells through granule membrane fusion (4). This is followed by the release of allergic inflammatory mediators, including histamine, chemokines, cytokines and eicosanoids for the change of membrane permeability (5). As a major allergic mediator, histamine is the most important molecule in acute allergy and acts by binding to the histamine H1 receptor, which manifests edema, warmth and erythema by causing vasodilation, increasing vascular permeability and leukocyte recruitment (6). Additionally, inflammatory cytokines such as tumor necrosis factor (TNF)‐α, interleukin (IL)‐1β and IL‐4, affect the chronic inflammatory phase by enhancing B cell survival or T cell activation (7). Furthermore, nuclear factor (NF)‐κB is an important transcriptional factor in inflammation and activated NF‐κB is able to regulate gene expression of inflammatory cytokine genes, including TNF‐α, IL-1β and IL‐4 (8). Finally, rat basophilic leukemia (RBL)‐2H3 cells are suitable for in vitro studies of mast cell‐mediated allergic inflammation, which involves the degranulation and expression of inflammatory cytokines (9,10). Angelica dahurica (A. dahurica; Fisch. ex Hoffm.) Benth. et Hook. f. ex Franch. et Sav (Umbelliferae) is a plant that belongs to the Angelica genus and is distributed in Northern and Northeastern China. In Traditional Chinese Medicine, the roots of A. dahurica have been used to treat headache, rhinitis, cold and toothache amongst others. Furthermore, pharmacological studies have shown that it has antimicrobial (11), hepatoprotective (12), antioxidative (13) and cholinesterase Coumarins from the roots of Angelica dahurica cause anti‐allergic inflammation
منابع مشابه
Super-oxidized solution inhibits IgE-antigen-induced degranulation and cytokine release in mast cells.
Activation of the high affinity IgE receptor (Fc epsilonRI) through IgE-antigen complexes induces mast cell degranulation, synthesis of lipid mediators and cytokine production. These effects are involved in Type I hypersensitivity reactions and controlling them has been the main objective of many anti-allergic therapies. Here we report that pretreatment of murine bone marrow derived mast cells ...
متن کاملRole of IgE Low-Affinity Receptor (CD23) in Pathogenesis of Nasal Polyp
Background: Nasal polyps, a common clinical problem, are characterized by eosinophilic and mast cell inflammation. The role of allergy and IgE in pathogenesis of nasal polyps is still unclear. IgE receptors are important components of the immunological pathway in allergic and inflammatory diseases. Objective: To determine if the low affinity IgE receptor (CD23) is presented on nasal polyp tis...
متن کاملEnhanced mast cell activation in mice deficient in the A2b adenosine receptor
Antigen-mediated cross-linking of IgE bound to mast cells via the high affinity receptor for IgE triggers a signaling cascade that results in the release of intracellular calcium stores, followed by an influx of extracellular calcium. The collective increase in intracellular calcium is critical to the release of the granular contents of the mast cell, which include the mediators of acute anaphy...
متن کاملProtein Profiling of the Secretome of FcεRI Activated RBL-2H3.1 Cells
Background: Secretory proteins of IgE receptor activated mast cells and basophils play a pivotal role in the generation of immediate and long term immune responses in allergy and type I hypersensitivity. Objective: The present study aims to generate a 2-D map and profile of proteins secreted from a high secretory variant of the rat basophilic leukemia cell line, RBL-2H3.1, which in view of the ...
متن کاملModulation of Immunoglobulin (Ig)E-mediated Systemic Anaphylaxis by Low-Affinity Fc Receptors for IgG
It is widely accepted that immunoglobulin (Ig)E triggers immediate hypersensitivity responses by activating a cognate high-affinity receptor, FcepsilonRI, leading to mast cell degranulation with release of vasoactive and proinflammatory mediators. This apparent specificity, however, is complicated by the ability of IgE to bind with low affinity to Fc receptors for IgG, FcgammaRII and III. We ha...
متن کامل