Traditional Chinese herbal (Kampo) medicines (Shohange-ka-bukuryo-to, Nichin-to, Rikkunshi-to, Hangeshashin-to, etc.) have frequently been used in empirical treatment of chronic hypofunction of the gastrointestinal system. Some patients who take these Kampo medicines have no organic disease such as peptic ulcer; reflex esophagitis or gastric cancer but have a condition classified as non-ulcer dyspepsia (NUD).1) Most NUD patients tend to have depressive and psychosomatic conditions and are exposed to continual affective stress.2) That continual stress causes abnormalities in the hypothalamo-pituitary-adrenal (HPA) axis and autonomic nervous function. 3,4) Sho-hange-ka-bukuryo-to, a Kampo medicine regulating gastrointestinal function, has been used to treat nausea, vomiting, acute and chronic gastritis and upper gastrointestinal abnormalities (gastric atony). It has been especially widely used to treat hyperemesis of pregnancy. Nichin-to also has been used to treat nausea and vomiting, and clinical difference between these two medicines is slight. Pinelliae Tuber and Zingiberis Rhizoma are herbs, both of which are included in Sho-hange-ka-bukuryo-to and Nichin-to, with antiemetic activity. 5,6) Therefore, the pharmacological effects of the two medicines might be due to the herbs.ACTH is a peptide containing 39 amino acids, and ACTHimmunoreactive substance (IS) is found in tissues other than the pituitary gland (i.e., brain, adrenal gland, gastrointestinal tract, pancreas, thyroid gland and placenta).7) The secretion of ACTH is controlled by the circadian rhythm mechanism and negative feedback from plasma cortisol and neurogenic stimulation. The peptide has secretory action of glucocorticoid and rises under stress.Cortisol, commonly used to indicate the level of stress, is secreted by the zona fasciculate of the adrenal cortex and its secretion is dependent on the ACTH level. In general, venipuncture for blood sampling is postulated to be a stress factor that can increase circulating ACTH and cortisol levels, etc. 8,9) Repetitive blood sampling places subjects under artificial stress and venipuncture as a stressor is useful for the evaluation of the pharmacological effects of drugs.10-12) Naito et al. reported other Kampo medicines (Rikkunshi-to, Hange-shashin-to, Hange-koboku-to) regulated plasma ACTH and cortisol levels under stress.13) These medicines also commonly included Pinelliae Tuber and Zingiberis Rhizoma.To determine whether the pharmacological effects of Shohange-ka-bukuryo-to and Nichin-to on stress-related hormone levels (ACTH and cortisol) under continual stress, and to determine the contribution of the herbs to the pharmacological effects of Kampo, we compared the plasma ACTH-IS and cortisol levels after administration of these Kampo medicines and related herbs.
MATERIALS AND METHODSMaterials Sho-hange-ka-bukuryo-to (EK-21, lot 1XC31), prepared as a 1.7 g dried powder extract of Pinelliae Tuber (6.0 g), Zingiberis Rhizoma (2.0 g) and Hoelen (5.0 g) were kindly supplied by Kanebo Co., Ltd. (Tokyo, Ja...