Saireito (TJ-114), a Japanese traditional herbal medicine, reduces 5-fluorouracil-induced intestinal mucositis in mice by inhibiting cytokine-mediated apoptosis in intestinal crypt cells.
Saireito (TJ-114), a Japanese traditional herbal medicine, reduces 5-fluorouracil-induced intestinal mucositis in mice by inhibiting cytokine-mediated apoptosis in intestinal crypt cells.
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DOI：
10.1371/journal.pone.0116213
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Kadowaki M
中科院分区：
文献类型：
--
作者：
Kato S;Hayashi S;Kitahara Y;Nagasawa K;Aono H;Shibata J;Utsumi D;Amagase K;Kadowaki M
临床化疗经常引起肠粘膜炎作为副作用，这是伴随着严重的腹泻。我们最近发现，在5-氟尿嘧啶（5-FU）诱导的肠粘膜炎的发展过程中，嘌呤介导的凋亡途径可能是重要的。Saireito是日本传统的草药（汉方），在日本被广泛用于治疗腹泻和各种炎症性疾病。在本研究中，我们研究了Saireito对5-FU诱导的小鼠肠粘膜炎的影响，特别是与肠腺细胞凋亡的关系。雄性C57 BL/6小鼠经腹膜内给予5-FU（50 mg/kg），每日一次，持续6天。肠粘膜炎进行了组织化学评价。Saireito（100-1000 mg/kg）经口给药。每日两次，共6天。重复5-FU治疗引起严重的肠粘膜炎，包括形态学损伤，伴有体重减轻和腹泻。每日服用saireito可降低肠粘膜炎的严重程度，且呈剂量依赖性。在5-FU治疗期间体重减轻和腹泻也被saireito给药显著减弱。在首次注射5-FU后24 h内，肠腺中凋亡细胞和caspase-3激活的细胞数量增加，并伴有肿瘤坏死因子（TNF）-α和白细胞介素（IL）-1β mRNA的上调。然而，所有这些措施后斋藤管理显着降低。这些结果表明，saireito减弱5-FU诱导的肠粘膜炎。这种作用可能来自于通过抑制炎性细胞因子的上调而减少肠隐窝中的细胞凋亡。因此，saireito可能在临床上用于预防癌症化疗期间的肠粘膜炎。
Clinical chemotherapy frequently causes intestinal mucositis as a side effect, which is accompanied by severe diarrhea. We recently showed that the cytokine-mediated apoptotic pathway might be important for the development of intestinal mucositis induced by 5-fluorouracil (5-FU). Saireito, the traditional Japanese herbal (Kampo) medicine, is widely used to treat diarrhea and various inflammatory diseases in Japan. In the present study, we investigated the effect of saireito on 5-FU-induced intestinal mucositis in mice, especially in relation to apoptosis in the intestinal crypt. Male C57BL/6 mice were given 5-FU (50 mg/kg), i.p. once daily for 6 days. Intestinal mucositis was evaluated histochemically. Saireito (100–1000 mg/kg) was administered p.o. twice daily for 6 days. Repeated 5-FU treatment caused severe intestinal mucositis including morphological damage, which was accompanied by body weight loss and diarrhea. Daily administration of saireito reduced the severity of intestinal mucositis in a dose-dependent manner. Body weight loss and diarrhea during 5-FU treatment were also significantly attenuated by saireito administration. The number of apoptotic and caspase-3-activated cells in the intestinal crypt was increased, and was accompanied by up-regulated tumor necrosis factor (TNF)-α and interleukin (IL)-1β mRNA within 24 h of the first 5-FU injection. However, all of these measures were significantly lower after saireito administration. These results suggest that saireito attenuates 5-FU-induced intestinal mucositis. This action may come from the reduction of apoptosis in the intestinal crypt via suppression of the up-regulation of inflammatory cytokines. Therefore, saireito may be clinically useful for the prevention of intestinal mucositis during cancer chemotherapy.
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