Magnolol inhibits leukotriene synthesis in rat basophilic leukemia-2H3 cells.
We have observed an inhibitory action of magnolol on the production of leukotriene (LT) C4 and LTB4, important lipid mediators in allergy and inflammation. IgE- and A23187-stimulated production of LTC4 and LTB4 was measured by radio-immunoassay (RIA) in the absence or presence of various concentrations of magnolol in intact rat basophilic leukemia (RBL)-2H3 cells. Magnolol dose-dependently inhibited synthesis of LTC4 and LTB4. Magnolol inhibited the IgE-mediated increase of intracellular calcium ion concentration, resulting in the inhibition of cytosolic phospholipase A2 (cPLA2) and possibly 5-lipoxygenase (5-LO), both calcium ion-dependent enzymes. In cell-free studies magnolol inhibited LTC4 synthase activity. LTA4 hydrolase activity was only inhibited at the higher concentration (2.5 x 10(-5)M). These results indicate that magnolol inhibits production of LTs by inhibiting PLA2, 5-LO, LTC4 synthase and LTA4 hydrolase which are essential for LT-synthesis. Magnolol may have anti-allergic effect by blocking LT-synthesis.
Hamasaki
Y
Y
Department of Pediatrics, Saga Medical School, Japan. hamasaki@post.saga-med.ac.jp
Kobayashi
I
I
Zaitu
M
M
Tsuji
K
K
Kita
M
M
Hayasaki
R
R
Muro
E
E
Yamamoto
S
S
Matsuo
M
M
Ichimaru
T
T
Miyazaki
S
S
D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004851:Epoxide Hydrolases / Q000037:antagonists & inhibitors; D005982:Glutathione Transferase / Q000037:antagonists & inhibitors; D015471:Leukemia, Basophilic, Acute / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D007975:Leukotriene B4 / Q000096:biosynthesis*; D017997:Leukotriene C4 / Q000096:biosynthesis*; D017705:Lignans; D016859:Lipoxygenase Inhibitors; D051381:Rats; D014407:Tumor Cells, Cultured
D001713:Biphenyl Compounds; D004791:Enzyme Inhibitors; D017705:Lignans; D016859:Lipoxygenase Inhibitors; C005498:magnolol; D007975:Leukotriene B4; D017997:Leukotriene C4; D005982:Glutathione Transferase; D004851:Epoxide Hydrolases; C041116:leukotriene-C4 synthase; C043134:leukotriene A4 hydrolase