中国科学院机构知识库网格
Chinese Academy of Sciences Institutional Repositories Grid
首页 机构 成果 学者
  
  1. CAS IR Grid
  2. 合肥物质科学研究院
  3. 中国科学院合肥物质科学研究院
Berberine attenuates 5-fluorouracil-induced intestinal mucosal injury by modulating the gut microbiota without compromising its anti-tumor efficacy

文献类型：期刊论文

作者Wu, Changhong1; Yang, Jie1; Ye, Chenxiao6; Wu, Hui1; Shu, Wenxi1; Li, Rongrong5; Wang, Sihan1; Lu, Yi2,7; Chen, Haitao3,7; Zhang, Zewei4
刊名HELIYON
出版日期2024-07-30
卷号10
关键词5-Fluorouracil Berberine Intestinal mucositis PI3K/AKT/mTOR pathway Intestinal flora
DOI10.1016/j.heliyon.2024.e34528
通讯作者Chen, Haitao(chenht2756@zjcc.org.cn) ; Zhang, Zewei(zhangzw@zjcc.org.cn) ; Yao, Qinghua(yaoqh@zjcc.org.cn)
英文摘要Background: 5-Fluorouracil (5-Fu), a prominent chemotherapeutic agent for colorectal cancer (CRC) treatment, is often associated with gastrointestinal toxicities, particularly diarrhea. Our previous study demonstrated that berberine (BBR) ameliorates 5-Fu-induced intestinal mucosal injury by modulating the gut microbiota in rats. Nevertheless, the precise molecular mechanism underlying BBR 's protective effect on intestinal mucosa remains elusive, and its impact on the anti-tumor efficacy of 5-Fu warrants further investigation. Methods: The effect of BBR on 5-Fu-induced intestinal mucosal injury was investigated using a tumor-bearing murine model, employing H &E staining, 16 S rDNA sequencing, transcriptome sequencing, Western blot analysis, cell experiments and constructing a pseudo-germ-free tumor xenograft model. Result: Our findings demonstrate that BBR alleviates intestinal mucosal damage, reduces the levels of inflammatory factors (IL-6, TNF- alpha, and IL-1 beta), and inhibits epithelial cell apoptosis in 5Fu-treated mice without compromising 5-Fu 's anti-tumor efficacy. Moreover, 16 S rDNA sequencing indicated that BBR significantly increases the abundance of Akkermansia and decreases the abundance of pathogenic bacteria Escherichia/Shigella at the genus level. Mechanistically, transcriptome sequencing and Western blot analysis confirmed that BBR upregulates PI3K/AKT/mTOR expression in the intestinal mucosa. However, this effect was not observed in tumor tissues. Notably, BBR did not demonstrate a direct protective effect on 5-Fu-treated CCD841 and SW480 cells. Additionally, BBR had no effect on the PI3K/AKT/mTOR pathway in the intestinal tissue of the 5-Fu-treated mouse model with a depleted gut microbiota. Conclusion: This study indicates that BBR alleviates 5-Fu-induced intestinal mucosal injury by modulating the gut microbiota and regulating the PI3K/AKT/mTOR signaling pathway without compromising the anti-tumor efficacy of 5-Fu.
WOS关键词COLORECTAL-CANCER ; COLON-CANCER ; CHEMOTHERAPY ; DIARRHEA ; THERAPY ; FLUOROURACIL ; TRIAL
资助项目Natural Science Foundation of Zhejiang province[LY21H290001] ; Natural Science Foundation of Zhejiang province[LQ22H290002] ; Traditional Chinese Medicine Research Program of Zhejiang Province[2023ZF003] ; Traditional Chinese Medicine Research Program of Zhejiang Province[2022ZA024] ; Key Project of Natural Science Foundation of Zhejiang Province[LZ20H290001] ; National Natural Science Foundation of China[82204823] ; National Natural Science Foundation of China[82074201] ; China Postdoctoral Science Foundation[2021M703485] ; Medical and Health Platform Program of Zhejiang Province[2021KY569] ; Medical and Health Platform Program of Zhejiang Province[2022RC109]
WOS研究方向Science & Technology - Other Topics
语种英语
WOS记录号WOS:001272914000001
出版者CELL PRESS
资助机构Natural Science Foundation of Zhejiang province ; Traditional Chinese Medicine Research Program of Zhejiang Province ; Key Project of Natural Science Foundation of Zhejiang Province ; National Natural Science Foundation of China ; China Postdoctoral Science Foundation ; Medical and Health Platform Program of Zhejiang Province
源URL[http://ir.hfcas.ac.cn:8080/handle/334002/137065]  
专题中国科学院合肥物质科学研究院
通讯作者Chen, Haitao; Zhang, Zewei; Yao, Qinghua
作者单位1.Zhejiang Chinese Med Univ, Sch Clin Med 2, Hangzhou 310053, Peoples R China
2.Chinese Acad Sci, Zhejiang Canc Hosp, Inst Basic Med & Canc IBMC, Dept Clin Nutr, Hangzhou 310022, Zhejiang, Peoples R China
3.Key Lab Tradit Chinese Med Zhejiang Prov, Integrated Tradit Chinese & Western Med Oncol Lab, Hangzhou 310022, Zhejiang, Peoples R China
4.Univ Chinese Acad Sci, Canc Hosp, Zhejiang Canc Hosp, Dept Hepatobiliary & Pancreat Surg, Hangzhou 310022, Zhejiang, Peoples R China
5.Zhejiang Chinese Med Univ, Affiliated Hosp 3, Hangzhou 310012, Zhejiang, Peoples R China
6.Zhejiang Chinese Med Univ, Sch Clin Med 1, Hangzhou 310053, Peoples R China
7.Chinese Acad Sci, Hangzhou Inst Med HIM, Zhejiang Canc Hosp, Hangzhou 310022, Zhejiang, Peoples R China
8.Zhejiang Chinese Med Univ, Affiliated Hosp 2, Xinhua Hosp Zhejiang Prov, Hangzhou 310005, Zhejiang, Peoples R China
推荐引用方式
GB/T 7714		 Wu, Changhong,Yang, Jie,Ye, Chenxiao,et al. Berberine attenuates 5-fluorouracil-induced intestinal mucosal injury by modulating the gut microbiota without compromising its anti-tumor efficacy[J]. HELIYON,2024,10.
APA Wu, Changhong.,Yang, Jie.,Ye, Chenxiao.,Wu, Hui.,Shu, Wenxi.,...&Yao, Qinghua.(2024).Berberine attenuates 5-fluorouracil-induced intestinal mucosal injury by modulating the gut microbiota without compromising its anti-tumor efficacy.HELIYON,10.
MLA Wu, Changhong,et al."Berberine attenuates 5-fluorouracil-induced intestinal mucosal injury by modulating the gut microbiota without compromising its anti-tumor efficacy".HELIYON 10(2024).

入库方式： OAI收割

来源：合肥物质科学研究院

浏览0
下载0
收藏0
其他版本

除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。