Figure 1.
Three-dimensional high-performance liquid chromatograph pattern of saireito (TJ-114).
Figure 2.
Effect of saireito and daikenchuto on changes in body weight and diarrhea during 5-fluorouracil (5-FU) treatment.
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. *P < 0.05 versus control (vehicle alone), # P < 0.05 versus normal (5-FU-untreated).
Figure 3.
Effect of saireito on shortening of villus height and crypt destruction induced by 5-fluorouracil (5-FU) in mouse small intestines.
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). The jejunum was excised on day 6, sectioned, and stained with H&E. Histological observations for intestinal villi (A, 100×) and crypts (B, 400×) were performed. The height of villi (C), the number of surviving crypts per millimeter (D), and surviving cells per crypt (E) were measured. Data are presented as the mean ± SEM of 6–8 mice. *P < 0.05, versus control (vehicle alone); # P < 0.05, versus normal (5-FU-untreated).
Figure 4.
Effect of saireito on apoptosis and caspase-3 activation in the intestinal crypt induced by 5-fluorouracil (5-FU).
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. *P < 0.05, versus control (vehicle alone); # P < 0.05, versus normal (5-FU-untreated).
Figure 5.
Effect of saireito on increased TNF-α and IL-1β mRNA expression induced by 5-fluorouracil (5-FU) in mouse small intestines.
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 and the expression of TNF-α (A) and IL-1β (B) mRNA was determined by quantitative RT-PCR. Data are presented as the mean ± SEM of 6 mice. *P < 0.05, versus control (vehicle alone); # P < 0.05, versus normal (5-FU-untreated).
Figure 6.
Effect of saireito on the suppression of cell proliferation induced by 5-fluorouracil (5-FU) in mouse small intestines.
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, sectioned, and Ki67 immunostaining was performed (A). The number of proliferative cells was counted (B). Data are presented as the mean ± SEM of 6 mice. # P < 0.05, versus normal (5-FU-untreated).
Figure 7.
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.
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. *P < 0.05, versus control (vehicle alone); # P < 0.05, versus normal (5-FU-untreated).