在2019年，结肠癌是日本癌症相关死亡的第二大原因。研究了从栀子（茜草科）中分离出的龙胆苦苷对于由氮异丙酰脲/硫酸葡萄糖酸钠（AOM/DSS）诱导的结肠肿瘤生长和结肠内白细胞介素（IL）-1β、单核细胞趋化蛋白（MCP）-1、IL-10和程序性细胞死亡1（PD-1）水平的影响。在第0天和第27天经腹腔给予10毫克/千克的AOM诱导结肠癌。在第7-15天、32-33天和35-38天，给予小鼠饮用1%（w/v）的DSS饮用水。龙胆苦苷（30和100毫克/千克）于第1-16天口服，停药11天（第16到26天），然后在第27-41天再次口服。采用酶联免疫吸附检测法（ELISA）测量了结肠内的细胞因子、趋化因子和PD-1水平。发现龙胆苦苷显著抑制了结肠肿瘤数量和面积的增加。此外，龙胆苦苷（100毫克/千克）将结肠内的IL-1β、MCP-1、PD-1和IL-10水平分别降低了67.4%、57.2%、100%和100%。龙胆苦苷显著减少了COX-2和TOX/TOX2阳性细胞的数目。龙胆苦苷（30和100毫克/千克）通过对免疫组织化学分析中的信号转导和转录激活因子3（STAT3）表达的磷酸化水平分别降低了64.2%和98.2%。因此，龙胆苦苷对结肠肿瘤生长的抑制作用可能与通过调节COX-2和TOX/TOX2的下调表达，通过抑制磷酸化STAT3表达（体内和体外）降低肠道中IL-1β、MCP-1、IL-10和PD-1的水平有关。版权所有©2023 Elsevier B.V.。保留所有权利。

Colon cancer was the second leading cause of cancer-related deaths in Japan in 2019. The effects of geniposide isolated from Gardenia jasminoides fructus (Rubiaceae) on the azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced growth of colon tumors and changes in interleukin (IL)-1 β, monocyte chemoattractant protein (MCP)-1, IL-10, and programmed cell death-1 (PD-1) levels in the colon were investigated. The intraperitoneal administration of AOM (10 mg/kg) on days 0 and 27 induced colorectal carcinogenesis. Free access to 1% (w/v) DSS drinking water was given to mice on days 7-15, 32-33, and 35-38. Geniposide (30 and 100 mg/kg) was orally administered on days 1-16, discontinued for 11 days (days 16 to 26), and then administered again on days 27-41. Colonic levels of cytokines, chemokine, and PD-1 were measured using by enzyme-linked immunosorbent assay (ELISA). Increases in colorectal tumor numbers and areas were significantly inhibited by geniposide. In addition, geniposide (100 mg/kg) reduced colonic levels of IL-1 β, MCP-1, PD-1 and IL-10 by 67.4, 57.2, 100%, and 100% respectively. Cyclooxygenase (COX)-2- and thymocyte selection high mobility group box proteins (TOX/TOX2)-positive cell numbers were significantly reduced by geniposide. Geniposide (30 and 100 mg/kg) decreased the phosphorylation of signal transducer and activator of transcription 3 (STAT3) expressions in immunohistochemical analysis by 64.2 and 98.2%, respectively. Thus, the inhibitory effects of geniposide on colon tumor growth may be associated with reductions in the colonic levels of IL-1 β, MCP-1, IL-10, and PD-1 via the down-regulated expression of COX-2 and TOX/TOX2 through the inhibition of Phospho-STAT3 expression (in vivo and in vitro).Copyright © 2023 Elsevier B.V. All rights reserved.