Flavoring agent dihydrocoumarin alleviates IgE-mediated mast cell activation and allergic inflammation

• Published in: Food & function Vol. 13; no. 6; pp. 3621 - 3631
• Main Authors: Xie, Chu-Chu, Zhang, Bo-Ping, Wang, Hui-Na, Li, Wei-Yong, Cai, Ze-Lang, He, Yong, Ji, Kunmei, Chen, Jia-Jie
• Format: Journal Article
• Language: English
• Published: England Royal Society of Chemistry 21.03.2022
• Subjects: Actin; Allergic diseases; Allergic reactions; Anaphylaxis; Antibodies; Antigens; Basophilic leukemia; Body temperature; Bone marrow; Cell activation; Degranulation; Effector cells; Elongation; Extravasation; Histamine; Human serum albumin; Hypersensitivity; Immunoglobulin E; In vivo methods and tests; Inflammation; Interleukin 4; Leukemia; MAP kinase; Mast cells; Molecular modelling; NF-κB protein; Ovalbumin; Passive cutaneous anaphylaxis; Serum albumin; Thickening; Transcription factors
• ISSN: 2042-6496; 2042-650X
• DOI: 10.1039/d2fo00190j

Mast cells (MCs) are the main effector cells in the onset of high-affinity receptor for IgE (Fc RI)-mediated allergic diseases. The aim of this study was to test whether dihydrocoumarin (DHC), a food flavoring agent derived from Melilotus officinalis , can block IgE-induced MC activation effects and to examine the potential molecular mechanisms by which DHC affects MC activation. Rat basophilic leukemia cells (RBLs) and mouse bone marrow-derived mast cells (BMMCs) were sensitized with anti-dinitrophenol (DNP) immunoglobulin (Ig)E antibodies, stimulated with DNP-human serum albumin antigen, and treated with DHC. Western blot analyses were performed to detect the expression of signaling proteins. Murine IgE-mediated passive cutaneous anaphylaxis (PCA) and ovalbumin (OVA)-induced active systemic anaphylaxis (ASA) models were used to examine DHC effects on allergic reactions in vivo . DHC inhibited MC degranulation, as evidenced by reduced β-hexosaminidase activity and histamine levels, and reduced morphological changes associated with MC activation, namely cellular elongation and F-actin reorganization. DHC inhibited the activation of MAPK, NF-κB, and AP-1 pathways in IgE-activated MCs. Additionally, DHC could attenuate IgE/Ag-induced allergic reactions (dye extravasation and ear thickening) in PCA as well as OVA challenge-induced reactions in ASA mice (body temperature, serum histamine and IL-4 secretion changes). In conclusion, DHC suppressed MC activation. DHC may represent a new MC-suppressing treatment strategy for the treatment of IgE-mediated allergic diseases. The flavoring agent dihydrocoumarin suppressed IgE-induced mast cell activation via down-regulating MAPK, NF-κB and AP-1 pathways. Dihydrocoumarin may represent a novel MC-suppressing strategy for the treatment of IgE-mediated allergic diseases.