Shimotsu-to is the agent in Juzen-taiho-to responsible for the prevention of endometrial carcinogenesis in mice

We have found that Juzen-taiho-to has a preventive effect on endometrial carcinogenesis in mice (Carcinogenesis 22 (2001) 587). In the present study, the constituents of Juzen-taiho-to responsible for this effect were explored using a short-term experiment. Thirty female ICR mice were divided into five groups: Group 1 was given a diet containing 0.2% of Juzen-taiho-to and 5 ppm estradiol-17β (E2); Group 2 was given a diet containing Shimotsu-to (0.07%) and E2 (5 ppm); Group 3 received Shikunshi-to (0.08%) and E2 (5 ppm) in the diet; Group 4 was given 5 ppm E2 in the diet; and Group 5 served as a control. Exposure of Juzen-taiho-to or Shimotsu-to decreased E2-stimulated expression of estrogen-related gene c-fos mRNA (P<0.05), and the cytokines interleukin-1α mRNA and tumor necrosis factor α mRNA P<0.01). A similar trend was not found upon treatment with Shikunshi-to. These findings suggest that Shimotsu-to is responsible for the inhibitory effects of Juzen-taiho-to on the estrogen-related endometrial carcinogenesis in mice.