Effect of Mao-Bushi-Saishin-to (Ma-Huang-Fu-Zi-Xi-Xin-Tang: MBS) on prostaglandin E(2) (PGE(2)) production was investigated using C6 rat glioma cells. Mao or Saishin inhibited histamine-induced PGE(2) production while MBS slightly decreased and Bushi increased it. MBS and Mao inhibited and Bushi enhanced A23187-induced PGE(2) production while Saishin had no effect. Concomitantly, Mao inhibted, but Bushi fascilitated, histamine- and A23187-induced phosphorylation of extracellular signal-regulated kinase (ERK)1/2. Treatment of MBS, Mao and also Saishin increased cAMP content. From these results, MBS inhibit PGE(2) production in C6 cells, mainly due to Mao but also due to Saishin at least in part, and the counteraction of Bushi. The former effect is mediated by formation of cAMP and resulting inhibition of ERK1/2-phosphorylation.