Several Japanese herbal medicines (Kampo), including Yokukansan, Yokukansankachimpihange, Shigyakusan, Kososan, Kamishoyosan, Kamikihito, Saikokaryukotsuboreito, Keishikaryukotsuboreito, Hangekobokuto, and Rikkunshito, are clinically used for patients with stress-related symptoms and diseases, according to the patient's constitution and symptoms (`Sho' in Oriental medicine). Kamikihito and Yokukansan are prescribed for the treatment of insomnia and neurosis in Japan. However, the precise mechanisms of actions of these products remain unclear. We investigated their possible antistress effects and involvement of oxytocin in the mechanisms of their actions in an animal model of stress. Oxytocin is a posterior pituitary hormone related to uterine contraction and milking. In recent years, its effects in the central nervous system-including its antistress effect-have been attracting interest. Oxytocin is reported to reduce stress levels via regulation of activities in the hypothalamic-pituitary-adrenal axis. Administration of Kamikihito or Yokukansan significantly increased the secretion of oxytocin in acute stress situations and exerted an antistress effect. Furthermore, the effects of these drugs were partially abrogated by administration of an oxytocin receptor antagonist. These results suggest that Kamikihito and Yokukansan have antistress activity and that increased oxytocin secretion may be involved in the mechanism underlying this effect. In clinical practice, the target candidates for these two drugs are different. Although both are used for irritability, anger and insomnia, Kamikihito is generally prescribed to patients who are physically weak, have weak digestive functions, or complain of mental anxiety. Yokukansan, on the other hand, is prescribed to patients with moderate physical strength, who are sensitive, and easily excited. These Kampo medicines may also be useful for stress-induced symptoms and illnesses.
