Clinopodium gracile inhibits mast cell-mediated allergic inflammation: involvement of calcium and nuclear factor-kappaB.
Mast cell-mediated allergic disease is involved in many diseases such as anaphylaxis, rhinitis, asthma and atopic dermatitis. The discovery of drugs for the treatment of allergic disease is an important subject in human health. In this study, we investigated the effect of the water extract of Clinopodium gracile Matsum var. multicaule (WECG) on the mast cell-mediated allergic inflammation and studied the possible mechanism of action. WECG inhibited compound 48/80-induced systemic anaphylaxis and immunoglobulin E-mediated cutaneous anaphylaxis in a dose-dependent manner. WECG dose-dependently reduced histamine release from rat peritoneal mast cells and human mast cells. The inhibitory effect of WECG on histamine release was mediated by the modulation of intracellular calcium. In addition, WECG attenuated the phorbol 12-myristate 13-acetate and calcium ionophore A23187-stimulated gene expression and secretion of proinflammatory cytokines such as tumor necrosis factor-alpha and interleukin-6 in human mast cells. The inhibitory effect of WECG on these proinflammatory cytokines was nuclear factor-kappaB (NF-kappaB) dependent. Our findings provide evidence that WECG inhibits mast cell-derived allergic inflammation and involvement of calcium and NF-kappaB in these effects.
Park
Seung-Bin
SB
CMRI, Department of Pharmacology, School of Medicine, Kyungpook National University Medical School, Daegu 700-422, South Korea.
Kim
Sang-Hyun
SH
Suk
Kyoungho
K
Lee
Hyun-Shik
HS
Kwon
Taeg Kyu
TK
Ju
Min-Gyu
MG
Jeon
Hoon
H
Kim
Dae-Keun
DK
Lim
Jong-Pil
JP
Shin
Tae-Yong
TY
D000707:Anaphylaxis / Q000139:chemically induced / Q000188:drug therapy; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006636:Histamine Release / Q000187:drug effects / Q000276:immunology; D006967:Hypersensitivity / Q000150:complications* / Q000188:drug therapy* / Q000378:metabolism; D007249:Inflammation / Q000150:complications / Q000188:drug therapy / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D019686:Lamiaceae / Q000737:chemistry*; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D008813:Mice, Inbred ICR; D016328:NF-kappa B / Q000378:metabolism*; D010323:Passive Cutaneous Anaphylaxis / Q000187:drug effects / Q000276:immunology; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D003189:p-Methoxy-N-methylphenethylamine
D016207:Cytokines; D018836:Inflammation Mediators; D016328:NF-kappa B; D010936:Plant Extracts; D003189:p-Methoxy-N-methylphenethylamine; D002118:Calcium