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三叶崖爬藤总黄酮通过调节肠道微生物群和代谢产物抑制结直肠癌生长。

Total flavonoids of Tetrastigma hemsleyanum Diels et Gilg inhibits colorectal tumor growth by modulating gut microbiota and metabolites.

作者信息

Han Bing, Zhai Yufei, Li Xuan, Zhao Huan, Sun Chengtao, Zeng Yuqing, Zhang Weiping, Lu Jinjian, Kai Guoyin

机构信息

Laboratory for Core Technology of TCM Quality Improvement and Transformation, College of Pharmaceutical Science, The Third Affiliated Hospital, Academy of Chinese Medical Science, Zhejiang Chinese Medical University, Hangzhou 310053, China.

State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao 999078, China.

出版信息

Food Chem. 2023 Jun 1;410:135361. doi: 10.1016/j.foodchem.2022.135361. Epub 2022 Dec 30.

Abstract

Tetrastigma hemsleyanum Diels et Gilg is a dietary supplement in southern China. The total flavonoids of T. hemsleyanum (THTF) can be used for gastrointestinal disease treatment. Colorectal cancer (CRC) is associated with gut microbiota dysbiosis. This study was designed to investigate the effect of THTF on CRC from gut microbiota and fecal metabolomics. THTF (120 mg/kg) oral gavage reduced tumor growth and protected intestinal function (p-p65/p65, ZO-1) in HCT116 xenografts. THTF increased probiotics Bifidobacteriales, Bifidobacteriaceae, Bifidobacterium, Bifidobacterium pseudolongum, and decreased "harmful" bacteria Bacteroidota, Firmicutes, Bacteroidia, Rikenellaceae, Odoribacter, Alistipes richness. Furthermore, THTF restored abnormal fecal metabolite levels. It showed a strong correlation among gut microbiota, metabolites, and tumor weight. Finally, THTF promoted Bifidobacterium pseudolongum growth in vitro, whose cell-free supernatant further inhibited HCT116 cell proliferation and clonogenicity. Together, THTF delays CRC tumor growth by maintaining microbiota homeostasis, restoring fecal metabolites, and protecting intestinal function.

摘要

三叶崖爬藤是中国南方的一种膳食补充剂。三叶崖爬藤总黄酮(THTF)可用于治疗胃肠道疾病。结直肠癌(CRC)与肠道微生物群失调有关。本研究旨在从肠道微生物群和粪便代谢组学方面探讨THTF对CRC的影响。THTF(120mg/kg)灌胃可抑制HCT116异种移植瘤的生长并保护肠道功能(p-p65/p65、紧密连接蛋白1)。THTF增加了益生菌双歧杆菌目、双歧杆菌科、双歧杆菌属、假长双歧杆菌的数量,并减少了“有害”细菌拟杆菌门、厚壁菌门、拟杆菌纲、理研菌科、气味杆菌属、艾氏菌属的数量。此外,THTF恢复了异常的粪便代谢物水平。它在肠道微生物群、代谢物和肿瘤重量之间显示出很强的相关性。最后,THTF在体外促进了假长双歧杆菌的生长,其无细胞上清液进一步抑制了HCT116细胞的增殖和克隆形成能力。总之,THTF通过维持微生物群稳态、恢复粪便代谢物和保护肠道功能来延缓CRC肿瘤的生长。

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