Abstract
Alisol B 23-acetate (AB23A), a natural triterpenoid, has been reported to exert hepatoprotective and antitumor activities. Aiming to investigate the anti-inflammatory activity, this study examined the effect of AB23A on mast cells and allergic reaction. AB23A inhibited the degranulation of mast cells stimulated by immunoglobulin E/antigen (IgE/Ag), and also decreased the synthesis of leukotriene C4 (LTC4), production of interlukin-6 (IL-6), and expression of cyclooxygenase-2 (COX-2) in a concentration-dependent manner with no significant cytotoxicity in bone marrow-derived mast cells (BMMCs). AB23A inhibited spleen tyrosine kinase (Syk) and the downstream signaling molecules including phospholipase Cγ (PLCγ), serine-threonine protein kinase/inhibitor of nuclear factor kappa-B kinase/nuclear factor kappa-B (Akt/IKK/NF-κB), and mitogen-activated protein kinases/cytosolic phospholipase A2 (MAPK/cPLA2). Furthermore, AB23A blocked mobilization of Ca2+. Similar results were obtained in other mast cell lines Rat basophilic leukemia (RBL)-2H3 cells and a human mast cell line (HMC-1). In addition, AB23A attenuated allergic responses in an acute allergy animal model, passive cutaneous anaphylaxis (PCA). Taken together, this study suggests that AB23A inhibits the activation of mast cells and ameliorates allergic reaction, and may become a lead compound for the treatment of mast cell-mediated allergic diseases.
Highlights
Mast cells play an important role in the initiation and propagation of various inflammatory disorders such as asthma, atopic dermatitis, arthritis, etc [1]
bone marrow-derived mast cells (BMMCs) were sensitized with immunoglobulin E (IgE) overnight, pre-treated with Alisol B 23-acetate (AB23A) for 1 h, and stimulated with anti-dinitrophenyl (DNP) IgE-human serum albumin (HSA) for 15 min
We demonstrated for the first time that AB23A diminished the degranulation in the immunoglobulin E/antigen (IgE/Ag)-stimulated BMMCs via inhibiting the FcεRI-mediated spleen tyrosine kinase (Syk) signal pathway
Summary
Mast cells play an important role in the initiation and propagation of various inflammatory disorders such as asthma, atopic dermatitis, arthritis, etc [1]. Interaction of a multivalent antigen with FcεRI induces the activation of the spleen tyrosine kinase (Syk), and phosphorylation of linker for activated T cell (LAT). These proteins serve as scaffolds for multi-molecular signaling complexes for the binding of cytosolic adapter molecules such as Gads, Grb, and SLP76, guanosine triphosphate exchangers including Sos and Vav, and the signaling enzymes phospholipase Cγ1 (PLCγ1) and PLCγ2 [4]. Activation of mitogen-activated protein kinases (MAPKs) enhances the production of arachidonic acid (AA) and its metabolites [5] These signals lead to mast cell degranulation, eicosanoid generation, and cytokine production
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