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Inhibitory effect of the Kampo medicinal formula Yokukansan on acute stress-induced defecation in rats

Authors Kanada Y, Katayama A, Ikemoto H, Takahashi K, Tsukada M, Nakamura A, Ishino S, Hisamitsu T, Sunagawa M

Received 11 November 2017

Accepted for publication 22 February 2018

Published 6 April 2018 Volume 2018:14 Pages 937—944

DOI https://doi.org/10.2147/NDT.S156795

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Prof. Dr. Roumen Kirov

Peer reviewer comments 3

Editor who approved publication: Dr Taro Kishi


Yasuaki Kanada, Ayami Katayama, Hideshi Ikemoto, Kana Takahashi, Mana Tsukada, Akio Nakamura, Shogo Ishino, Tadashi Hisamitsu, Masataka Sunagawa

Department of Physiology, School of Medicine, Showa University, Shinagawa-ku, Tokyo, Japan

Objectives: Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder with symptoms of abnormal defecation and abdominal discomfort. Psychological factors are well known to be involved in onset and exacerbation of IBS. A few studies have reported effectiveness of traditional herbal (Kampo) medicines in IBS treatment. Yokukansan (YKS) has been shown to have anti-stress and anxiolytic effects. We investigated the effect of YKS on defecation induced by stress and involvement of oxytocin (OT), a peptide hormone produced by the hypothalamus, in order to elucidate the mechanism of YKS action.
Methods and results: Male Wistar rats were divided into four groups; control, YKS (300 mg/kg PO)-treated non-stress (YKS), acute stress (Stress), and YKS (300 mg/kg PO)-treated acute stress (Stress+YKS) groups. Rats in the Stress and Stress+YKS groups were exposed to a 15-min psychological stress procedure involving novel environmental stress. Levels of plasma OT in the YKS group were significantly higher compared with those in the Control group (P < 0.05), and OT levels in the Stress+YKS group were remarkably higher than those in the other groups (P < 0.01). Next, rats were divided into four groups; Stress, Stress+YKS, Atosiban (OT receptor antagonist; 1 mg/kg IP)-treated Stress+YKS (Stress+YKS+B), and OT (0.04 mg/kg IP)-treated acute stress (Stress+OT) groups. Rats were exposed to acute stress as in the previous experiment, and defecation during the stress load was measured. Administration of YKS or OT significantly inhibited defecation; however, administration of Atosiban partially abolished the inhibitory effect of YKS. Finally, direct action of YKS on motility of isolated colon was assessed. YKS (1 mg/mL, 5 mg/mL) did not inhibit spontaneous contraction.
Conclusion: These results suggested that YKS influences stress-induced defecation and that increased OT secretion may be a mechanism underlying this phenomenon.

Keywords: Yokukansan, oxytocin, irritable bowel syndrome, acute stress, corticosterone, Kampo medicine

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