Coptisine Suppresses Mast Cell Degranulation and Ovalbumin-Induced Allergic Rhinitis

Abstract

Coptisine is one of the main components of isoquinoline alkaloids in the coptidis rhizome. The effect of coptisine on allergic rhinitis has not been investigated. In this study, we report the effects and mechanisms of coptisine using monoclonal anti-2,4,6-dinitrophenyl-immunoglobulin (Ig) E/human serum albumin (DNP-IgE/HSA)-stimulated rat basophilic leukemia cells (RBL-2H3 cells) in vitro and an ovalbumin (OVA)-induced allergic rhinitis (AR) in mice. The results showed that coptisine markedly decreased the levels of β-hexosaminidase, histamine, interleukin (IL)-4, and tumor necrosis factor (TNF)-α. Coptisine also prevented morphological changes, such as restoring an elongated shape, inhibiting granule release on toluidine blue staining, and reorganizing inhibited filamentous actins (F-actin). Additionally, coptisine blocked the phosphorylation of phosphoinositide3-kinase (PI3K)/Akt (as known as protein kinase B(PKB)) in RBL-2H3 cell. Furthermore, the results showed that coptisine suppressed OVA-induced allergic rhinitis symptoms, such as nasal rubbing and OVA-specific IgE, and histamine, IL-4 and TNF-α levels in the serum of AR mice. These data suggested that coptisine should have inhibitory effects on the inflammatory responses of mast cells, and may be beneficial for the development of coptisine as a potential anti-allergic drug.

Aurora kinase inhibitor tozasertib suppresses mast cell activation in vitro and in vivo

“…Membrane structure changes in activated mast cells have been shown to follow the cross‐linking of cell surface receptors by external antigens (Briggs, 1963), the redistribution of actin filaments (Deng et al, 2009), and decoupling of the cytoskeleton from the plasma membrane ( Draber et al, 2012). The inhibition of mast cell activation by tozasertib in vitro appeared to be similar to that induced by coptisine, a cytotoxic alkaloid used in traditional Chinese medicine, shown to prevent granule release and F‐actin reorganization (Fu et al, 2018).…”

“…The mixture was discarded, and the fixed cells were stained with 300 μl of toluidine blue dye (1% w/v in 0.9% NaCl solution, pH 2.5) for 30 min. Images of the stained cells were examined for heterochromatin particles with an inverted microscope (Carl Zeiss, Goettingen, Germany; Fu, Ni, Wang, & Hong, 2018; Kruger & Bloom, 1974).…”

Coptisine fromCoptis chinensisexerts diverse beneficial properties: A concise review

“…It was observed that coptisine (1‐30 μmol/L, 15 minutes‐24 hours) inhibited LPS‐induced inflammatory response in Raw 264.7 macrophages which was attributed by coptisine‐mediated blocking of NF‐κB, MAPK and PI3K/AKT pathway signalling transduction . Coptisine (10‐30 μmol/L, 12 hours) was also reported to decrease productions of histamine, IL‐4 and TNF‐α in (DNP‐IgE/HSA)‐stimulated rat RBL‐2H3 cells by suppressing PI3K/Akt phosphorylation . The findings of Zhou et al demonstrated that coptisine treatment reversed IL‐1β‐induced p‐p65 mRNA/protein overexpression and IκBα degradation in OA chondrocyte .…”

“…Similarly, inhibition of inflammatory process was also observed in animal models including xylene‐induced ear oedema, carrageenan‐elicited paw oedema, LPS‐induced shock, OVA‐induced allergic rhinitis and MSU‐elicited gouty after coptisine administration . Mechanistically, coptisine (50‐200 mg/kg, oral, once daily for 10 days; 10‐40 mg/kg, oral, once daily for 7 days; 2.91‐11.61 mg/kg, i.v, single dose, 0‐24 hours) diminished cytokine production through blocking inflammatory transduction mediated by the phosphorylation of IKKα/β and MAPK subfamilies, the translocation and degradation of p65 in oedema tissue as well as suppression of NLRP3 inflammasome activation . Of interest, coptisine (0.97‐3.87 mg/kg, i.v; single dose, 0‐4 hours) showed no effect on the up‐regulation of oedema skin temperature induced by carrageenan subcutaneously injection in rats .…”

“…Red arrows represent for decreased expression and/or activity; blue arrows represent for increased expression and/or activity kg, i.v, single dose, 0-24 hours) diminished cytokine production through blocking inflammatory transduction mediated by the phosphorylation of IKKα/β and MAPK subfamilies, the translocation and degradation of p65 in oedema tissue as well as suppression of NLRP3 inflammasome activation. 50,53,55 Of interest, coptisine (0.97-3.87 mg/kg, i.v; single dose, 0-4 hours) showed no effect on the up-regulation of oedema skin temperature induced by carrageenan subcutaneously injection in rats. 49 Furthermore, there is a study investigating a pharmacokinetic-pharmacodynamic model for coptisine challenge of inflammation in LPS-elicited rats, and authors emphasized early stage of TNF-α response is the key factor of the subsequent inflammatory cascade.…”