Immunoinformatics Study of Procyanidins as Mast Cell Stabilizers

Abstract

Background:Allergens are foreign proteins that stimulate the production of immunoglobulin E (IgE), when they come in contact with human body. These allergens after binding with IgE through FcεRI receptor, triggers the signal transduction reaction in mast cell and basophil cells, leading to allergic reactions by releasing some mediators. Mast cell stabilizer block mast cell degranulation, stabilizing the cell and thereby preventing the release of histamine 8 and related mediators e.g. leukotrienes (for basophils) and prostaglandin D2 and IL-5 (for mast cells) during hypersensitivity reaction. Though innumerable synthetic mast cell stabilizers are present 9 in our medicinal science, but the search for suitable natural product as mast cell stabilizer is still going on. 10 Comparative study shows that higher efficiency for natural product quercetin than synthetic compound cromolyn for inhibiting allergic reactions.11 Several inhibitors of IgE:FcεRI binding have been identified e.g. an anti-IgE therapeutic antibody (omalizumab) , an engineered protein inhibitor, DARPin E2_799-11, which are used to treat severe allergic asthma. 12,13 Polyphenols which are abundant in apple are proven effective for allergic rhinitis treatment by preventing degranulation of granulocytes in mast cells. 14,15,16 Procyanidins are polymeric form of catechins. In apple, almost 50% to 60% polyphenols are oligomers and polymers of catechins.Dimeric catechins are procyanidin B1, B2, C1 present in apple extract shows antiallergic activity on rhinitis treatment. Among them, procyanidin C1 extracted from unripe apples (Rosaceae mal- 815 lus) shows anti-allergic effect by various mechanisms e.g. FcεRI induced degranulation and cytokine production of mast cells. Procyanidin C1 which is related with intra-cellular signalling pathway,prevents FcεRI-mediated mast cell activation. 17 The flow cytometric study is confirmed that polymeric procyanidins supress the binding of IgE antibody to FcεRI.17 But the molecular mechanism for inhibitory effect on antibody IgE with FcεRI binding is unknown to all. A compound must have an anti-allergic activity if it inhibits the binding between Ig E antibody and FcεRI receptor during type I hypersensitivity reaction. Comparative studies on different procyanidins structures and physicochemical properties using computational methods will help us to identify apple extract, as herbal medicine in allergic reactions. Computational docking studies are used to elaborate the mechanism of action of various natural products e.g. quercetin glycosides as inhibitor of angiotensinconverting enzyme for the treatment of myocardial infarction 18 and fatty acids of black cumin oil as inhibitors of P-glycoprotein to improve pharmaceutics of many lifesaving drugs. 19 MATERIALS AND METHODS X-ray crystallographic structures for human IgE, FcεRIreceptorThe three-dimensional structure of IgE (PDBID 4J4P) and FcεRI receptor (PDBID 1F2Q) are downloaded from the RCSB protein Data Bank. 20 2D and 3D structures of procyanidin B1, B2, C1 an...

Augmentation of Mast Cell Stability, a Therapeutic Strategy for Idiopathic Pulmonary Fibrosis

“…Essentially, based on the outcome of recent pre-clinical studies, some active agents have been recognized that have preventive potential against animal models of IPF along with interesting facts related to ability to alter mast cell degranulation via different mechanisms. These antifibrotic agents included adenylyl cyclase activators, β-adenoreceptor agonists, flavonoids, mast cell stabilizers, phosphodiesterase inhibitors and procyanidins [50][51][52][53][54][55][56][57][58][59][60][61][62][63][64][65][66][67][68][69] . The antifibrotic actions of these agents have been reported at initial and pre-clinical stages as discussed below.…”

“…Chemically, these are oligomeric flavonoids and oligomers of catechin, epicatechin and their gallic acid esters. Recently, procyanidin C1 type has been identified as natural antiallergic agent, which has possibility to stabilize mast cell during allergic reaction by altering the binding affinity of IgE with FcεRI receptor [68] . In vivo study of proanthocyanidin indicated that, it could inhibit inflammatory cell infiltrations and fibrosis as well as decrease hydroxyproline content [69] .…”

Immunoinformatics Based Study of T Cell Epitopes in Zea m 1 Pollen Allergen

“…To prevent the type I hypersensitivity reaction, drugs known as mast cell stabilizers e.g., synthetic, semi synthetic and natural stabilizers, can be used as therapeutic agents. These mast cell stabilizers obtained from natural resources can be classified into different groups such as flavonoids, coumarins, phenols [12], terpenoids, alkaloids etc. Considering their mechanisms of action, mast cell stabilizers can be classified as Ca 2+ channel blocking agents, suppressors of gene expression of genes (tumor necrosis factor alpha, different interleukins), inhibitors for phosphorylation reactions in MAPK, ERK, JNK Gab2 signaling pathways, down regulators of enzyme histidine dicarboxylase, suppressors of mRNA of CD23, inhibitors of COX2/5 lipooxygenase enzyme, inhibitors of prostaglandin D 2 synthesis, LTC 4 inhibitors, and Spleen tyrosin kinase enzyme inhibitors [13].…”