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

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-1β, IL-8, and IL-13. Furthermore, IMP inhibited the phosphorylation levels of Syk, Lyn, PLC-γ1, and Gab2, as well as the downstream MAPK, PI3K/AKT, and NF-κB 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-κB, and Nrf2/HO-1 pathways.

Coumarins as Modulators of the Keap1/Nrf2/ARE Signaling Pathway

“…Hu et al reported that IMP-induced Nrf2 activation effectively upregulated its downstream antioxidants, possibly offering cellular protection to the heart from injury induced by arsenic trioxide (As 2 O 3 ) [76]. Very recently, Xian et al investigated the protective effect of IMP against excess ROS and chronic airway inflammation in OA-administered mice [77]. Treatment with IMP suppressed ROS, proinflammatory cytokines, inflammatory cell infiltration, collagen deposition, and goblet cell hyperplasia.…”

“…Treatment with IMP suppressed ROS, proinflammatory cytokines, inflammatory cell infiltration, collagen deposition, and goblet cell hyperplasia. These effects have been suggested to be mediated via modulation of Nrf2 signaling following IMP administration [77].…”

Inhibitory Effects of Eriodictyol-7-O-β-d-glucuronide and 5,7-Dihydroxy-4-chromene Isolated from Chrysanthemum zawadskii var. latilobum in FcεRI-Mediated Human Basophilic KU812F Cell Activation

“…FcεRI is a high-affinity IgE receptor expressed on the cell surface of mast cells and basophils [9][10][11]. Recently, much attention has been focused on searching for biologically active antiallergic compounds that downregulate FcεRI expression [12,22,23]. Our results showed that EDG and DC induced a decrease in protein, and that the mRNA levels of the cellular FcεRI α-chain may be associated with the suppression of cell-surface FcεRI expression ( Figure 3).…”

“…The downregulation of FcεRI expression in effector cells may lead to the attenuation of IgE-mediated allergic reaction. The signaling pathways of MAPK and NF-kB are predominant cascades that are closely related to allergic responses [12]. Chrysanthemum zawadskii var.…”

FcεRI-HDAC3-MCP1 Signaling Axis Promotes Passive Anaphylaxis Mediated by Cellular Interactions

“…Sodium butyrate, an inhibitor of HDACs, can decrease levels of ovalbumin-specific IgE and improve clinical symptoms and nasal mucosa epithelial morphology in a mouse model of allergic rhinitis [86]. PCA reactions can increase expression levels of inflammatory cytokines via the activation of PI3K/AKT, MAPK and NF-κB [87]. HDAC inhibitors such as TSA can inhibit PCA and TpCR [15].…”