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

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.

• Authors: Dong Eun Kim, Kyoung-Jin Min, Min-Jong Kim, Sang-Hyun Kim, Taeg Kyu Kwon
• Journal: Molecules (Basel, Switzerland) (Molecules) Vol. 24 Issue 11 (Jun 05 2019) ISSN: 1420-3049 [Electronic] Switzerland
• PMID: 31195760 (Publication Type: Journal Article)

Chemical References

• Cytokines
• Flavones
• Inflammation Mediators
• Immunoglobulin E
• JNK Mitogen-Activated Protein Kinases
• hispidulin

Topics

• Animals
• Cell Degranulation (drug effects)
• Cytokines (metabolism)
• Down-Regulation (drug effects)
• Flavones (chemistry, pharmacology, therapeutic use)
• Histamine Release (drug effects)
• Hypersensitivity (complications, drug therapy)
• Immunoglobulin E (metabolism)
• Inflammation (complications, drug therapy, pathology)
• Inflammation Mediators (metabolism)
• JNK Mitogen-Activated Protein Kinases (metabolism)
• Male
• Mast Cells (drug effects, pathology)
• Mice, Inbred ICR
• Passive Cutaneous Anaphylaxis (drug effects)
• Phosphorylation (drug effects)