The traditional Japanese medicine Rikkunshito increases the plasma level of ghrelin in humans and mice.
OBJECTIVE
Rikkunshito is a traditional Japanese medicine that is widely used for treating upper gastrointestinal symptoms. Our purpose is to clarify the effect of Rikkunshito on the levels of peptide hormones and cytokines in healthy humans and mice.


METHODS
We administered Rikkunshito, 7.5 g per day, to 21 healthy volunteers for 2 weeks and examined the changes in plasma peptide and hormone levels. In mice, we administered free access to water containing 0, 0.7, 1.1, and 1.4% Rikkunshito for 2 weeks and examined the changes in plasma peptide levels and ghrelin mRNA expression levels in the stomach.


RESULTS
Plasma acylated ghrelin levels at 0, 2, and 6 weeks after the start of administration were 6.7 +/- 2.8, 11.7 +/- 4.0, and 10.5 +/- 4.4 fmol/ml, respectively. The levels at 2 and 6 weeks were significantly higher than that at 0 time (p < 0.01, paired t test). The levels of interleukin 4, interferon gamma, and granulocyte colony-stimulating factor in plasma decreased significantly (p < 0.01) after the administration of Rikkunshito. In mice, the levels of plasma acylated ghrelin changed in proportion to the concentration of Rikkunshito in drinking water, and it was revealed by quantitative RT-PCR that the ghrelin mRNA expression level in the stomach was up-regulated.


CONCLUSIONS
Rikkunshito increased the plasma acylated ghrelin level in healthy volunteers and normal mice. Additionally, this change was maintained for at least 4 weeks after the end of administration. In mice, Rikkunshito increased the ghrelin mRNA expression level in the stomach.
Matsumura
Tomoaki
T
Department of Medicine and Clinical Oncology (K1), Graduate School of Medicine, Chiba University, Inohana 1-8-1, Chiba, 260-8670, Japan.
Arai
Makoto
M
Yonemitsu
Yutaka
Y
Maruoka
Daisuke
D
Tanaka
Takeshi
T
Suzuki
Takuto
T
Yoshikawa
Masaharu
M
Imazeki
Fumio
F
Yokosuka
Osamu
O
D000328:Adult; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism; D054439:Ghrelin / Q000097:blood / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D007564:Japan; D008297:Male; D020835:Medicine, Kampo; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013270:Stomach / Q000187:drug effects*; D013997:Time Factors; D015854:Up-Regulation / Q000187:drug effects
D004365:Drugs, Chinese Herbal; D054439:Ghrelin; D012333:RNA, Messenger; C084136:liu-jun-zi-tang