Hispidulin Inhibits Mast Cell-Mediated Allergic Inflammation through Down-Regulation of Histamine Release and Inflammatory Cytokines.

Dong Eun Kim,Min-Jong Kim,Taeg Kyu Kwon,Kyoung-Jin Min,Sang-Hyun Kim

doi:10.3390/molecules24112131

Dong Eun Kim, Min-Jong Kim + Show 3 more

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https://doi.org/10.3390/molecules24112131

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Abstract

Hispidulin (4′,5,7-trihydroxy-6-methoxyflavone) is a natural compound derived from traditional Chinese medicinal herbs, and it is known to have an anti-inflammatory effect. Here, we investigated the effect of hispidulin on the immunoglobulin E (IgE)-mediated allergic responses in rat basophilic leukemia (RBL)-2H3 mast cells. When RBL-2H3 cells were sensitized with anti-dinitrophenyl (anti-DNP) IgE and subsequently stimulated with DNP-human serum albumin (HSA), histamine and β-hexosaminidase were released from the cells by degranulation of activated mast cells. However, pretreatment with hispidulin before the stimulation of DNP-HSA markedly attenuated release of both in anti-DNP IgE-sensitized cells. Furthermore, we investigated whether hispidulin inhibits anti-DNP IgE and DNP-HSA-induced passive cutaneous anaphylaxis (PCA), as an animal model for Type I allergies. Hispidulin markedly decreased the PCA reaction and allergic edema of ears in mice. In addition, activated RBL-2H3 cells induced the expression of inflammatory cytokines (tumor necrosis factor-α and interleukin-4), which are critical for the pathogenesis of allergic disease, through the activation of c-Jun N-terminal kinase (JNK). Inhibition of JNK activation by hispidulin treatment reduced the induction of cytokine expression in the activated mast cells. Our results indicate that hispidulin might be a possible therapeutic candidate for allergic inflammatory diseases through the suppression of degranulation and inflammatory cytokines expression.

Highlights

Mast cells are one of the major immune cells, and are distributed in blood vessels, lymphoid organs, and external environment such as in skin, lungs, urogenital tracts and gastrointestinal tracts [1].Mast cells protect our body from the damage by environmental dangers, and induce the inflammatory response [2]
Mast cells produce histamine, which is a key molecule in allergic responses
Inhibition rat basophilic Mast leukemia (RBL)-2H3 cells are issuitable cells to examine the effects of mast cell-mediated of histamine release mast cells is atouseful therapeutic target for the treatment of allergic symptoms

Summary

Introduction

Mast cells are one of the major immune cells, and are distributed in blood vessels, lymphoid organs, and external environment such as in skin, lungs, urogenital tracts and gastrointestinal tracts [1].Mast cells protect our body from the damage by environmental dangers, and induce the inflammatory response [2]. Mast cells activated by various stimuli release histamines, proteoglycans, serotonin, and lipid mediators (prostaglandins and leukotrienes) [3]. These mediators are accumulated within granules and are released into the extracellular environment by stimuli, resulting in the induction of inflammation and the recruitment of other immune cells, such as neutrophils, eosinophils, basophils, and monocyte/macrophages [4]. Mast cells synthesize and secrete other pro-inflammatory cytokines (interleukins, GM-CSF, and TGF-β) and chemokines [5]. These inflammatory reactions by mast cells are closely related to allergic reactions.

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