Licochalcones suppress degranulation by decreasing the intracellular Ca2+ level and tyrosine phosphorylation of ERK in RBL-2H3 cells.
Mast cells play a key role in allergic inflammation by releasing various mediators, such as histamine, serotonin, leukotrienes and cytokines. A signaling cascade of events activated by stimulation with antigens contributes to the regulation of mast cell degranulation. While various anti-inflammatory and anti-allergic drugs have been developed that inhibit degranulation of mast cells, the inhibitory mechanism has been poorly understood. Licochalcone A (Lico A) is a retrochalcone isolated from the root of Xinjiang liquorice and has been reported to exhibit various biological activities such as anti-inflammatory activity. We examined the effects of Lico A and related chalcones on degranulation in a rat basophilic leukemia cell line, RBL-2H3. Whereas Lico A and licochalcone C (Lico C) exhibited inhibitory activity with cytotoxicity, licochalcone D (Lico D) significantly inhibited the degranulation in RBL-2H3 cells with low cytotoxicity. Moreover, Lico D significantly inhibited the Ca2+ influx and phosphorylation of extracellular signal regulated kinase (ERK) and MEK. These results suggest that Lico D inhibits mast cell degranulation via the inhibition of both extracellular Ca2+ influx and activation of the MEK-ERK pathway.
Tanifuji
Shota
S
Department of Biochemistry, Faculty of Pharmacy, Keio University, 1-5-30 Shibakoen, Minato-ku, Tokyo 105-8512, Japan.
Aizu-Yokota
Eriko
E
Funakoshi-Tago
Megumi
M
Sonoda
Yoshiko
Y
Inoue
Hideo
H
Kasahara
Tadashi
T
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D001491:Basophils / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D002118:Calcium / Q000378:metabolism; D015550:Cell Degranulation / Q000187:drug effects; D045744:Cell Line, Tumor; D047188:Chalcones / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D019610:Cytoprotection; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000378:metabolism*; D006035:Glycyrrhiza / Q000276:immunology; D042541:Intracellular Space / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D008517:Phytotherapy; D018517:Plant Roots; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D013329:Structure-Activity Relationship; D014443:Tyrosine / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D047188:Chalcones; D014443:Tyrosine; D048049:Extracellular Signal-Regulated MAP Kinases; C070840:licochalcone A; D002118:Calcium