Tagami Keiko, Niwa Kenji, Lian Zenglin, Gao Jingchun, Mori Hideki, Tamaya Teruhiko
Department of Obstetrics and Gynecology, Gifu University School of Medicine, 40 Tsukasa-machi, Gifu 500-8705, Japan.
Biol Pharm Bull. 2004 Feb;27(2):156-61. doi: 10.1248/bpb.27.156.
Juzen-taiho-to, a Kampo formula, originally consists of a mixture of Shimotsu-to and Shikunshi-to formulas together with two other crude ingredients. Juzen-taiho-to is reported to have a preventive effect on endometrial carcinogenesis in mice. Shimotsu-to exerts an inhibitory effect on estrogen-induced expression of c-fos, interleukin (IL)-1alpha and tumor necrosis factor (TNF)-alpha in uteri of ovarectomized mice. In the present study, short- and long-term experiments were designed to determine the effects of Juzen-taiho-to and Shimotsu-to on the estrogen-related endometrial carcinogenesis in mouse uteri, associated with the expression of cyclooxygenase (COX)-1 and -2. In the short-term experiment, exposure to Juzen-taiho-to or Shimotsu-to significantly reduced estradiol-17beta (E(2))-stimulated expressions of COX-2 mRNA (p<0.05) as well as the protein. However, no effects on the expression of COX-1 were observed. Shikunshi-to did not affect COX expression. In the long-term experiment, 90 female ICR mice were given N-methyl-N-nitrosourea (MNU) into their uterine corpora. The animals were divided into four groups as follows: group 1, a diet containing 0.07% Shimotsu-to and 5 ppm E(2); group 2, a diet containing 5 ppm E(2); group 3, a diet containing 0.07% Shimotsu-to; group 4 served as a control. Exposure of Shimotsu-to reduced the incidence of MNU- and E(2)-induced endometrial adenocarcinoma and atypical hyperplasia at the termination of the experiment (30 weeks). The above findings and our previous reports suggest that Shimotsu-to is responsible for the preventive effects of Juzen-taiho-to on estrogen-related endometrial carcinogenesis in mice, through the inhibition of estrogen-related COX-2 as well as c-fos, IL-1alpha and TNF-alpha expressions.
十全大补汤是一种汉方制剂，最初由四物汤和四君子汤配方与另外两种天然成分混合而成。据报道，十全大补汤对小鼠子宫内膜癌发生具有预防作用。四物汤对去卵巢小鼠子宫中雌激素诱导的c-fos、白细胞介素（IL）-1α和肿瘤坏死因子（TNF）-α表达具有抑制作用。在本研究中，设计了短期和长期实验，以确定十全大补汤和四物汤对小鼠子宫中与雌激素相关的子宫内膜癌发生的影响，以及与环氧化酶（COX）-1和-2表达的关系。在短期实验中，给予十全大补汤或四物汤显著降低了雌二醇-17β（E₂）刺激的COX-2 mRNA表达（p<0.05）以及蛋白质表达。然而，未观察到对COX-1表达的影响。四君子汤对COX表达无影响。在长期实验中，90只雌性ICR小鼠子宫体注射N-甲基-N-亚硝基脲（MNU）。将动物分为四组如下：第1组，含0.07%四物汤和5 ppm E₂的饮食；第2组，含5 ppm E₂的饮食；第3组，含0.07%四物汤的饮食；第4组作为对照。在实验结束时（30周），给予四物汤可降低MNU和E₂诱导的子宫内膜腺癌和非典型增生的发生率。上述发现及我们之前的报告表明，四物汤通过抑制雌激素相关的COX-2以及c-fos、IL-1α和TNF-α表达，对十全大补汤预防小鼠雌激素相关子宫内膜癌发生起到作用。
