The Chinese herbal medicine, Shinpi-To, inhibits IgE-mediated leukotriene synthesis in rat basophilic leukemia-2H3 cells

Abstract 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 LTC 4 and LTB 4 were measured by radioimmunoassay (RIA). Shinpi-To significantly inhibited IgE-mediated synthesis of leukotriene (LT)C 4 and LTB 4 . To identify the inhibitory sites, we investigated the action of this extract on four synthetic enzymes, phospholipase A 2 (PLA 2 ), 5-lipoxygenase (5-LO), LTC 4 synthase, and LTA 4 hydrolase. Shinpi-To inhibited the A23187-stimulated release of [ 3 H]arachidonic acid (AA) from the cell membrane, reflecting an effect on PLA 2 activity. It also suppressed production of LTC 4 and LTB 4 when cell lysates were incubated with AA as substrate. It did not inhibit the production of LTC 4 and LTB 4 when LTA 4 -free acid was used as the substrate. Shinpi-To did not inhibit the IgE-mediated increase of intracellular Ca 2+ ([Ca 2+ ] i ) concentration. Results indicate that Shinpi-To inhibits LT synthesis by inhibiting PLA 2 and 5-LO activities without affecting the mobilization of [Ca 2+ ] i .