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)C-4 and LTB4. 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), LTC4 synthase, and LTA(4) hydrolase. Shinpi-To inhibited the A23187-stimulated release of [H-3]arachidonic acid (AA) from the cell membrane, reflecting an effect on PLA(2) 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 LTA(4)-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 PLA(2) and 5-LO activities without affecting the mobilization of [Ca2+](i). (C) 1997 Elsevier Science Ireland Ltd.