Effect of saireito on apoptosis and caspase-3 activation in the intestinal crypt induced by 5-fluorouracil (5-FU).

<p>5-FU (50 mg/kg) was injected i.p. while saireito (1000 mg/kg) was administered p.o. twice, 30 min before and 8 h after 5-FU injection. The jejunum was excised 24 h after 5-FU injection, sectioned, and TUNEL assay (A, 400×) and cleaved-caspases-3 immunostaining (B, 400×) were performed. The number of apoptotic (C) and caspase-3-activated cells (D) were counted. Data are presented as the mean ± SEM of 6 mice. *<i>P < 0.05</i>, versus control (vehicle alone); ^#<i>P < 0.05</i>, versus normal (5-FU-untreated).</p

Three-dimensional high-performance liquid chromatograph pattern of saireito (TJ-114).

<p>Three-dimensional high-performance liquid chromatograph pattern of saireito (TJ-114).</p

Effect of saireito on the anti-tumor action, body weight loss, and diarrhea induced during 5-fluorouracil (5-FU) treatment in Colon 38 tumor-implanted mice.

<p>5-FU (20 mg/kg) was injected i.p. once daily for 6 days (days 7–12), while saireito (1000 mg/kg) was administered p.o. twice daily for 14 days (days 7–21), starting 7 day after tumor implantation. The volume (mm³) of solid tumor (A), body weight (B), and diarrhea score (C) were determined every 2 or 3 days, starting 7 days after the implantation. Data are presented as the mean ± SEM of 6–8 mice. *<i>P < 0.05</i>, versus control (vehicle alone); ^#<i>P < 0.05</i>, versus normal (5-FU-untreated).</p

Effect of saireito and daikenchuto on changes in body weight and diarrhea during 5-fluorouracil (5-FU) treatment.

<p>5-FU (50 mg/kg) was injected i.p. once daily while saireito (100–1000 mg/kg) and daikenchuto (2700 mg/kg) were administered p.o. twice daily for 6 days (days 0–5). Body weight is shown as a percentage of initial body weight (A), whereas the severity of diarrhea is scored using the four-grade scale (0 to 3) (B). Data are presented as the mean ± SEM of 6–8 mice. *<i>P < 0.05</i> versus control (vehicle alone), ^#<i>P < 0.05</i> versus normal (5-FU-untreated).</p

Data_Sheet_1_Repeated psychological stress, chronic vicarious social defeat stress, evokes irritable bowel syndrome-like symptoms in mice.PDF

Increasing evidence has demonstrated that emotional states and intestinal conditions are inter-connected in so-called “brain–gut interactions.” Indeed, many psychiatric disorders are accompanied by gastrointestinal symptoms, such as the irritable bowel syndrome (IBS). However, the functional connection remains elusive, partly because there are few useful experimental animal models. Here, we focused on a highly validated animal model of stress-induced psychiatric disorders, such as depression, known as the chronic vicarious social defeat stress (cVSDS) model mice, which we prepared using exposure to repeated psychological stress, thereafter examining their intestinal conditions. In the charcoal meal test and the capsaicin-induced hyperalgesia test, cVSDS model mice showed a significantly higher intestinal transit ratio and increased visceral pain-related behaviors, respectively. These changes persisted over one month after the stress session. On the other hand, the pathological evaluations of the histological and inflammatory scores of naive and cVSDS model mice did not differ. Furthermore, keishikashakuyakuto—a kampo medicine clinically used for the treatment of IBS—normalized the intestinal motility change in cVSDS model mice. Our results indicate that cVSDS model mice present IBS-like symptoms such as chronic intestinal peristaltic changes and abdominal hyperalgesia without organic lesion. We therefore propose the cVSDS paradigm as a novel animal model of IBS with wide validity, elucidating the correlation between depressive states and intestinal abnormalities.</p