1. Imperatorin Suppresses Anaphylactic Reaction and IgE-Mediated Allergic Responses by Inhibiting Multiple Steps of FceRI Signaling in Mast Cells: IMP Alleviates Allergic Responses in PCA.
- Author
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Xian Z, Jin G, Li H, Jiang J, Wang C, Zhu L, Jin Z, Li L, Piao H, Zheng M, and Yan G
- Subjects
- Animals, Cell Degranulation drug effects, Cell Line, Cytokines metabolism, Female, Hypersensitivity metabolism, Intracellular Signaling Peptides and Proteins metabolism, Mice, Mice, Inbred BALB C, NF-kappa B metabolism, Phosphatidylinositol 3-Kinases metabolism, Phospholipase C gamma metabolism, Phosphorylation drug effects, Protein-Tyrosine Kinases metabolism, Rats, Sprague-Dawley, Syk Kinase metabolism, Tumor Necrosis Factor-alpha metabolism, Furocoumarins pharmacology, Hypersensitivity drug therapy, Immunoglobulin E metabolism, Mast Cells drug effects, Passive Cutaneous Anaphylaxis drug effects, Signal Transduction drug effects
- Abstract
This study is to investigate the effects of imperatorin (IMP) on allergic responses mediated by mast cells, both in vitro and in vivo . Passive cutaneous anaphylaxis (PCA) model was established. Histological detection was performed to assess the ear histology. ELISA and Western blot analysis were used to detect the levels of corresponding cytokines and signalling pathway proteins. IMP decreased the leakage of Evans blue and the ear thickness in the PCA models, in a dose-dependent manner, and alleviated the degranulation of mast cells. Moreover, IMP reduced the expression of TNF- α , IL-4, IL-1 β , IL-8, and IL-13. Furthermore, IMP inhibited the phosphorylation levels of Syk, Lyn, PLC- γ 1, and Gab2, as well as the downstream MAPK, PI3K/AKT, and NF- κ B signaling pathways. In addition, IMP inhibited the mast cell-mediated allergic responses through the Nrf2/HO-1 pathway. IMP attenuates the allergic responses through inhibiting the degranulation and decreasing the expression levels of proinflammatory cytokines in the mast cells, involving the PI3K/Akt, MAPK, NF- κ B, and Nrf2/HO-1 pathways.
- Published
- 2019
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