Luteolin isolated from the flowers of Lonicera japonica suppresses inflammatory mediator release by blocking NF-kappaB and MAPKs activation pathways in HMC-1 cells.
Luteolin (3',4',5,7-tetrahydroxylflavone) is a plant flavonoid and pharmacologically active agent that has been isolated from several plant species. In the present study, the effect of luteolin from the flowers of Lonicera japonica on phorbol 12-myristate 13-acetate (PMA) plus A23187-induced mast cell activation was examined. Luteolin significantly inhibited the induction of inflammatory cytokines such as tumor necrosis factor (TNF)-alpha, interleukin (IL)-8, IL-6 and granulocyte-macrophage colony-stimulating factor (GM-CSF) by PMA plus A23187. Moreover, luteolin attenuated cyclooxygenase (COX)-2 expression and intracellular Ca2+ levels. In activated HMC-1 cells, the phosphorylation of extra-signal response kinase (ERK 1/2) and c-jun N-terminal Kinase (JNK 1/2), but not p38 mitogen-activated protein kinase (p38 MAPK) were decreased by treatment of the cells with luteolin. Luteolin inhibited PMA plus A23187-induced nuclear factor (NF)-kappaB activation, IkappaB degradation, and luciferase activity. Furthermore, luteolin suppressed the expression of TNF-alpha, IL-8, IL-6, GM-CSF, and COX-2 through a decrease in the intracellular Ca2+ levels, and also showed a suppression of the ERK 1/2, JNK 1/2, and NF-kappaB activation. These results indicated that luteolin from the flowers of Lonicera japonica exerted a regulatory effect on mast cell-mediated inflammatory diseases, such as RA, allergy disease and IBD.
Kang
Ok-Hwa
OH
Department of Oriental Pharmacy, College of Pharmacy, Wonkwang University, Wonkwang Oriental Medicines Research Institute, Jeonbuk 570-749, Korea.
Choi
Jang-Gi
JG
Lee
John-Hwa
JH
Kwon
Dong-Yeul
DY
D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D035264:Flowers / Q000737:chemistry*; D005786:Gene Expression Regulation; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D031239:Lonicera / Q000737:chemistry*; D047311:Luteolin / Q000302:isolation & purification* / Q000494:pharmacology*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D016207:Cytokines; D018836:Inflammation Mediators; D016328:NF-kappa B; D012333:RNA, Messenger; D000001:Calcimycin; D051546:Cyclooxygenase 2; D020928:Mitogen-Activated Protein Kinases; D047311:Luteolin; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium