Licarin A is a candidate compound for the treatment of immediate hypersensitivity via inhibition of rat mast cell line RBL-2H3 cells.

Abstract

OBJECTIVES:

We previously demonstrated that some phenylpropanoids are capable of inhibiting activated mast cells. This study evaluated the anti-allergic effects of licarin A, a neolignan isolated from various plants, on antigen-stimulated rat mast cell line.

METHODS:

The inhibitory effects of licarin A on histamine release, tumour necrosis factor-α (TNF-α) and prostaglandin D2 (PGD2) production, and cyclooxygenase-2 (COX-2) expression in dinitrophenyl-human serum albumin (DNP-HSA) rat basophilic leukemia cells (DNP-HSA-stimulated RBL-2H3 cells), were investigated by spectrofluorometry, ELISA and immunoblotting.

KEY FINDINGS:

Licarin A significantly and dose-dependently reduced TNF-α production (IC50 12.6 ± 0.3 μm) in DNP-HSA-stimulated RBL-2H3 cells. Furthermore, the levels of PGD2 secretion in DNP-HSA-stimulated cells pretreated with licarin A were lower than those stimulated with DNP-HSA alone (positive control). Treatment with licarin A at 20 μm produced slight suppression of DNP-HSA-induced increases in COX-2 mRNA and protein levels. We identified several signalling pathways that mediated these pharmacological effects. Licarin A treatment tended to reduce phosphorylated protein kinase C alpha/beta II (PKCα/βII) and p38 mitogen-activated protein kinase (MAPK) protein levels.

CONCLUSIONS:

Our results demonstrate that licarin A reduces TNF-α and PGD2 secretion via the inhibition of PKCα/βII and p38 MAPK pathways; this compound may be useful for attenuating immediate hypersensitivity.

• Authors: Takuya Matsui, Chihiro Ito, Satoru Masubuchi, Masataka Itoigawa
• Journal: The Journal of pharmacy and pharmacology (J Pharm Pharmacol) Vol. 67 Issue 12 Pg. 1723-32 (Dec 2015) ISSN: 2042-7158 [Electronic] England
• PMID: 26376734 (Publication Type: Journal Article)
• Copyright: © 2015 Royal Pharmaceutical Society.

Chemical References

• Anti-Allergic Agents
• Dinitrophenols
• Lignans
• Serum Albumin
• Tumor Necrosis Factor-alpha
• dinitrophenyl-human serum albumin conjugate
• licarin A
• Cyclooxygenase 2
• Ptgs2 protein, rat
• Protein Kinase C beta
• Protein Kinase C-alpha
• p38 Mitogen-Activated Protein Kinases
• Prostaglandin D2

Topics

• Animals
• Anti-Allergic Agents (pharmacology)
• Cell Line, Tumor
• Cyclooxygenase 2 (genetics, metabolism)
• Dinitrophenols (immunology)
• Dose-Response Relationship, Drug
• Enzyme Activation
• Histamine Release (drug effects)
• Hypersensitivity, Immediate (drug therapy, genetics, immunology, metabolism)
• Lignans (pharmacology)
• Mast Cells (drug effects, immunology, metabolism)
• Phosphorylation
• Prostaglandin D2 (metabolism)
• Protein Kinase C beta (metabolism)
• Protein Kinase C-alpha (metabolism)
• Rats
• Serum Albumin (immunology)
• Signal Transduction (drug effects)
• Time Factors
• Tumor Necrosis Factor-alpha (metabolism)
• p38 Mitogen-Activated Protein Kinases (metabolism)