Effect of Shimotsu-to (a Kampo medicine, Si-Wu-Tang) and its constituents on triphasic skin reaction in passively sensitized mice.

Previous studies have reported that mice passively sensitized with anti-DNP (dinitrophenol) IgE antibody exhibited IgE-mediated skin reaction with an immediate phase response (IPR) at 1 h and a late phase response (LPR) at 24 h after the challenge of DNFB (dinitrofluorobenzene). We recently found that a third phase inflammatory reaction with intense and persisting infiltration of eosinophils, named very late phase response (vLPR), was induced by DNFB challenge peaking at 8 days. In this study, we examined the effects of a Kampo medicine, Shimotsu-to (Si-Wu-Tang), and its constituent crude drugs on triphasic skin reaction in passively sensitized mice. Shimotsu-to inhibited ear swelling in LPR and vLPR after DNFB challenge in a dose-dependent manner, and slightly diminished the scratching behavior considered to be associated with pruritus in IPR. The inhibitory effect on LPR and vLPR was partly due to Cnidii Rhizoma (Senkyu) in Shimotsu-to formulation, especially its fraction 5 containing cnidilide. On the other hand, Angelicae Radix (Toki) rather than Cnidii Rhizoma (Senkyu) in Shimotsu-to, inhibited the scratching behavior, although it did not inhibit the ear swelling in IPR. These findings indicate that the Shimotsu-to formulation is useful for the inhibition of cutaneous inflammatory diseases.