Ginsenoside Rk3 modulates gut microbiota and regulates immune response of group 3 innate lymphoid cells to against colorectal tumorigenesis

Xue Bai; Rongzhan Fu; Yannan Liu; Jianjun Deng; Qiang Fei; Zhiguang Duan; Chenhui Zhu; Daidi Fan

doi:10.1016/j.jpha.2023.09.010

Volume 14 Issue 2

Feb. 2024

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Xue Bai, Rongzhan Fu, Yannan Liu, Jianjun Deng, Qiang Fei, Zhiguang Duan, Chenhui Zhu, Daidi Fan. Ginsenoside Rk3 modulates gut microbiota and regulates immune response of group 3 innate lymphoid cells to against colorectal tumorigenesis[J]. Journal of Pharmaceutical Analysis, 2024, 14(2): 259-275. doi: 10.1016/j.jpha.2023.09.010

Citation:

Xue Bai, Rongzhan Fu, Yannan Liu, Jianjun Deng, Qiang Fei, Zhiguang Duan, Chenhui Zhu, Daidi Fan. Ginsenoside Rk3 modulates gut microbiota and regulates immune response of group 3 innate lymphoid cells to against colorectal tumorigenesis[J]. Journal of Pharmaceutical Analysis, 2024, 14(2): 259-275. doi: 10.1016/j.jpha.2023.09.010

Citation:

Xue Bai, Rongzhan Fu, Yannan Liu, Jianjun Deng, Qiang Fei, Zhiguang Duan, Chenhui Zhu, Daidi Fan. Ginsenoside Rk3 modulates gut microbiota and regulates immune response of group 3 innate lymphoid cells to against colorectal tumorigenesis[J]. Journal of Pharmaceutical Analysis, 2024, 14(2): 259-275. doi: 10.1016/j.jpha.2023.09.010

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Ginsenoside Rk3 modulates gut microbiota and regulates immune response of group 3 innate lymphoid cells to against colorectal tumorigenesis

doi: 10.1016/j.jpha.2023.09.010

Xue Bai^a,b,
Rongzhan Fu^a,b,
Yannan Liu^a,b,
Jianjun Deng^a,b,
Qiang Fei^c,
Zhiguang Duan^a,b,
Chenhui Zhu^{a,b
,
,},
Daidi Fan^{a,b
,
,}

a. Shaanxi Key Laboratory of Degradable Biomedical Materials, School of Chemical Engineering, Northwest University, Xi'an, 710069, China;
b. Biotech & Biomed Research Institute, Northwest University, Xi'an, 710069, China;
c. School of Chemical Engineering and Technology, Xi'an Jiaotong University, Xi'an, 710069, China

Funds:

This work was supported by the National Key Research and Development Program, China (Grant Nos.: 2021YFC2101500 and 2021YFC2103900), the National Natural Science Foundation of China (Grant Nos.: 22278335 and 21978236), and the Natural Science Basic Research Program of Shaanxi, China (Grant No.: 2023-JC-JQ-17).

Received Date: May 16, 2023
Accepted Date: Sep. 18, 2023
Rev Recd Date: Aug. 25, 2023
Publish Date: Feb. 29, 2024

Abstract

Abstract

The gut microbiota plays a pivotal role in the immunomodulatory and protumorigenic microenvironment of colorectal cancer (CRC). However, the effect of ginsenoside Rk3 (Rk3) on CRC and gut microbiota remains unclear. Therefore, the purpose of this study is to explore the potential effect of Rk3 on CRC from the perspective of gut microbiota and immune regulation. Our results reveal that treatment with Rk3 significantly suppresses the formation of colon tumors, repairs intestinal barrier damage, and regulates the gut microbiota imbalance caused by CRC, including enrichment of probiotics such as Akkermansia muciniphila and Barnesiella intestinihominis, and clearance of pathogenic Desulfovibrio. Subsequent metabolomics data demonstrate that Rk3 can modulate the metabolism of amino acids and bile acids, particularly by upregulating glutamine, which has the potential to regulate the immune response. Furthermore, we elucidate the regulatory effects of Rk3 on chemokines and inflammatory factors associated with group 3 innate lymphoid cells (ILC3s) and T helper 17 (Th17) signaling pathways, which inhibits the hyperactivation of the Janus kinase-signal transducer and activator of transcription 3 (JAK-STAT3) signaling pathway. These results indicate that Rk3 modulates gut microbiota, regulates ILC3s immune response, and inhibits the JAK-STAT3 signaling pathway to suppress the development of colon tumors. More importantly, the results of fecal microbiota transplantation suggest that the inhibitory effect of Rk3 on colon tumors and its regulation of ILC3 immune responses are mediated by the gut microbiota. In summary, these findings emphasize that Rk3 can be utilized as a regulator of the gut microbiota for the prevention and treatment of CRC.
- Colorectal cancer,
- Ginsenoside,
- Immune cells,
- Gut microbiota

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References(52)

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