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 granu lar extract of seven Chinese medicinal herbs that is used in treating childhood asthma, on the leukotriene synthesis in rat basophilic leuke mia-2H3 cells (RBL-2H3 cells). IgE-loaded cells were stimulated with a nti-IgE serum in the presence or absence of Shinpi-To. Released LTC4 a nd LTB4 were measured by radioimmunoassay (RIA). Shinpi-To significant ly inhibited IgE-mediated synthesis of leukotriene (LT)C-4 and LTB4. T o identify the inhibitory sites, we investigated the action of this ex tract on four synthetic enzymes, phospholipase A(2) (PLA(2)), 5-lipoxy genase (5-LO), LTC4 synthase, and LTA(4) hydrolase. Shinpi-To inhibite d the A23187-stimulated release of [H-3]arachidonic acid (AA) from the cell membrane, reflecting an effect on PLA(2) activity. It also suppr essed production of LTC4 and LTB4 when cell lysates were incubated wit h AA as substrate. It did not inhibit the production of LTC4 and LTB4 when LTA(4)-free acid was used as the substrate. Shinpi-To did not inh ibit the IgE-mediated increase of intracellular Ca2+ ([Ca2+](i)) conce ntration. Results indicate that Shinpi-To inhibits LT synthesis by inh ibiting PLA(2) and 5-LO activities without affecting the mobilization of [Ca2+](i). (C) 1997 Elsevier Science Ireland Ltd.