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

Abstract

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

Acknowledgments

The authors are grateful to Tsumura & Co. for generously providing YKS and to Prof Guo Shi-yu for generously providing instructions for recording colonic motility.

Author contributions

All authors made substantial contributions to conception and design, acquisition of data, or analysis and interpretation of data; took part in drafting the article or revising it critically for important intellectual content; gave final approval of the version to be published; and agree to be accountable for all aspects of the work.

Disclosure

The authors report no conflicts of interest in this work.