The Chinese herbal medicine, shinpi-to, inhibits IgE-mediated leukotriene synthesis in rat basophilic leukemia-2H3 cells.
We examined the action of Shinpi-To (Formula divinita; TJ-85), a granular extract of seven Chinese medicinal herbs that is used in treating childhood asthma, on the leukotriene synthesis in rat basophilic leukemia-2H3 cells (RBL-2H3 cells). IgE-loaded cells were stimulated with anti-IgE serum in the presence or absence of Shinpi-To. Released LTC4 and LTB4 were measured by radioimmunoassay (RIA). Shinpi-To significantly inhibited IgE-mediated synthesis of leukotriene (LT)C4 and LTB4. To identify the inhibitory sites, we investigated the action of this extract on four synthetic enzymes, phospholipase A2 (PLA2), 5-lipoxygenase (5-LO). LTC4 synthase, and LTA4 hydrolase. Shinpi-To inhibited the A23187-stimulated release of [3H]arachidonic acid (AA) from the cell membrane, reflecting an effect on PLA2 activity. It also suppressed production of LTC4 and LTB4 when cell lysates were incubated with AA as substrate. It did not inhibit the production of LTC4 and LTB4 when LTA4-free acid was used as the substrate. Shinpi-To did not inhibit the IgE-mediated increase of intracellular Ca2+ ([Ca2+]i) concentration. Results indicate that Shinpi-To inhibits LT synthesis by inhibiting PLA2 and 5-LO activities without affecting the mobilization of [Ca2+]i.
Hamasaki
Y
Y
Department of Pediatrics, Saga Medical School, Saga-City, Japan.
Kobayashi
I
I
Hayasaki
R
R
Zaitu
M
M
Muro
E
E
Yamamoto
S
S
Ichimaru
T
T
Miyazaki
S
S
D000704:Analysis of Variance; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D001249:Asthma / Q000188:drug therapy; D001993:Bronchodilator Agents / Q000494:pharmacology; D000001:Calcimycin / Q000633:toxicity; D002118:Calcium / Q000378:metabolism; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D004365:Drugs, Chinese Herbal / Q000494:pharmacology* / Q000627:therapeutic use; D004809:Ephedrine / Q000031:analogs & derivatives / Q000494:pharmacology; D007073:Immunoglobulin E / Q000276:immunology*; D007476:Ionophores / Q000633:toxicity; D007553:Isotope Labeling; D015471:Leukemia, Basophilic, Acute / Q000473:pathology; D017572:Leukotriene A4 / Q000096:biosynthesis; D007975:Leukotriene B4 / Q000096:biosynthesis* / Q000378:metabolism; D017997:Leukotriene C4 / Q000096:biosynthesis* / Q000378:metabolism; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D010741:Phospholipases A / Q000037:antagonists & inhibitors; D054467:Phospholipases A2; D011863:Radioimmunoassay; D051381:Rats; D014316:Tritium; D014407:Tumor Cells, Cultured
D001993:Bronchodilator Agents; D004365:Drugs, Chinese Herbal; D007476:Ionophores; D017572:Leukotriene A4; D016859:Lipoxygenase Inhibitors; D014316:Tritium; D007975:Leukotriene B4; D016718:Arachidonic Acid; D017997:Leukotriene C4; D007073:Immunoglobulin E; D000001:Calcimycin; C041707:N-methylephedrine; D010741:Phospholipases A; D054467:Phospholipases A2; D004809:Ephedrine; D002118:Calcium