Yokukansan, a traditional Japanese herbal medicine, alleviates the emotional abnormality induced by maladaptation to stress in mice

• Published in: Phytomedicine (Stuttgart) Vol. 21; no. 3; pp. 363 - 371
• Main Authors: Tsuji, Minoru, Takeuchi, Tomoko, Miyagawa, Kazuya, Ishii, Daisuke, Imai, Taro, Takeda, Kotaro, Kitajima, Masaki, Takeda, Hiroshi
• Format: Journal Article
• Language: English
• Published: Germany Elsevier GmbH 15-02-2014; Urban & Fischer Verlag
• Subjects: Adaptation, Psychological; Animals; Care and treatment; Drugs, Chinese Herbal - pharmacology; Drugs, Chinese Herbal - therapeutic use; Emotional behavior; Health aspects; Hole-board; Magnoliopsida; Male; Medical research; Medicinal plants; Medicine, Experimental; Mental illness; Mice; Mice, Inbred ICR; Mouse; Phytochemistry; Phytotherapy; Piperazines - pharmacology; Poria; Restraint stress; Restraint, Physical; Serotonin 5-HT1 Receptor Agonists - pharmacology; Stress adaptation; Stress, Psychological - drug therapy; Stress, Psychological - etiology; Yokukansan; Emotional behavior; Hole-board; Restraint stress; Yokukansan; Stress adaptation; Mouse
• ISSN: 0944-7113; 1618-095X
• DOI: 10.1016/j.phymed.2013.08.025

The aim of the present study was to examine the effect of yokukansan, a traditional Japanese herbal medicine that is composed of Atractylodis lanceae Rhizoma, Poria, Cnidii Rhizoma, Uncariae Uncis cum Ramulus, Angelicae Radix, Bupleuri Radix and Glycyrrhizae Radix, on the emotional abnormality induced by maladaptation to stress in mice. Mice were exposed to repeated restraint stress for 60 or 240min/day for 14 days. From the 3rd day of stress exposure, mice were given yokukansan orally (p.o.) or the 5-HT1A receptor agonist flesinoxan intraperitoneally (i.p.) immediately after the daily exposure to restraint stress. After the final exposure to restraint stress, the emotionality of mice was evaluated using an automatic hole-board apparatus. A single exposure to restraint stress for 60min induced a decrease in head-dipping behavior in the hole-board test. This emotional stress response disappeared in mice that had been exposed to repeated restraint stress for 60min/day for 14 days, which confirmed the development of stress adaptation. In contrast, mice that were exposed to restraint stress for 240min/day for 14 days did not develop this stress adaptation, and still showed a decrease in head-dipping behavior. The decreased emotionality observed in stress-maladaptive mice was significantly recovered by chronic treatment with yokukansan (1000mg/kg, p.o.) as well as flesinoxan (0.25 and 0.5mg/kg, i.p.) immediately after daily exposure to stress. These findings suggest that yokukansan may have a beneficial effect on stress adaptation and alleviate the emotional abnormality under conditions of excessive stress.