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Ginsenoside Rh4 inhibits colorectal cancer via the modulation of gut microbiota-mediated bile acid metabolism.
Bai, Xue; Duan, Zhiguang; Deng, Jianjun; Zhang, Zhuo; Fu, Rongzhan; Zhu, Chenhui; Fan, Daidi.
Afiliação
  • Bai X; Engineering Research Center of Western Resource Innovation Medicine Green Manufacturing, Ministry of Education, School of Chemical Engineering, Northwest University, Xi'an, 710069, China; Biotech. & Biomed. Research Institute, Northwest University, Xi'an, 710069, China.
  • Duan Z; Engineering Research Center of Western Resource Innovation Medicine Green Manufacturing, Ministry of Education, School of Chemical Engineering, Northwest University, Xi'an, 710069, China; Biotech. & Biomed. Research Institute, Northwest University, Xi'an, 710069, China.
  • Deng J; Engineering Research Center of Western Resource Innovation Medicine Green Manufacturing, Ministry of Education, School of Chemical Engineering, Northwest University, Xi'an, 710069, China; Biotech. & Biomed. Research Institute, Northwest University, Xi'an, 710069, China.
  • Zhang Z; Plastic and Cosmetic Maxillofacial Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, 710061, China.
  • Fu R; Engineering Research Center of Western Resource Innovation Medicine Green Manufacturing, Ministry of Education, School of Chemical Engineering, Northwest University, Xi'an, 710069, China; Biotech. & Biomed. Research Institute, Northwest University, Xi'an, 710069, China. Electronic address: rongz
  • Zhu C; Engineering Research Center of Western Resource Innovation Medicine Green Manufacturing, Ministry of Education, School of Chemical Engineering, Northwest University, Xi'an, 710069, China; Biotech. & Biomed. Research Institute, Northwest University, Xi'an, 710069, China. Electronic address: zch20
  • Fan D; Engineering Research Center of Western Resource Innovation Medicine Green Manufacturing, Ministry of Education, School of Chemical Engineering, Northwest University, Xi'an, 710069, China; Biotech. & Biomed. Research Institute, Northwest University, Xi'an, 710069, China. Electronic address: fanda
J Adv Res ; 2024 Jul 03.
Article em En | MEDLINE | ID: mdl-38969093
ABSTRACT

INTRODUCTION:

Dysbiosis of the gut microbiota is emerging as a pivotal factor in the pathogenesis of colorectal cancer (CRC). Ginsenoside Rh4 (Rh4) is an active compound isolated from ginseng with beneficial effects in modulating intestinal inflammation and gut microbiota dysbiosis, but how Rh4 regulates the gut microbiota to alleviate CRC remains underexplored.

OBJECTIVES:

We investigated the impact of Rh4 on CRC and the mechanism of its action in inhibiting CRC via modulation of gut microbiota.

METHODS:

We used the AOM/DSS model and employed transcriptomics, genomics and metabolomics techniques to explore the inhibitory impact of Rh4 on CRC. Furthermore, we employed experiments involving antibiotic treatment and fecal microbiota transplantation (FMT) to investigate the role of the gut microbiota. Finally, we elucidated the pivotal role of key functional bacteria and metabolites regulated by Rh4 in CRC.

RESULTS:

Our research findings indicated that Rh4 repaired intestinal barrier damage caused by CRC, alleviated intestinal inflammation, and inhibited the development of CRC. Additionally, Rh4 inhibited CRC in a gut microbiota-dependent manner. Rh4 increased the diversity of gut microbiota, enriched the probiotic Akkermansia muciniphila (A. muciniphila), and alleviated gut microbiota dysbiosis caused by CRC. Subsequently, Rh4 regulated A. muciniphila-mediated bile acid metabolism. A. muciniphila promoted the production of UDCA by enhancing the activity of 7α-hydroxysteroid dehydrogenase (7α-HSDH). UDCA further activated FXR, modulated the TLR4-NF-κB signaling pathway, thus inhibiting the development of CRC.

CONCLUSION:

Our results confirm that Rh4 inhibits CRC in a gut microbiota-dependent manner by modulating gut microbiota-mediated bile acid metabolism and promoting the production of UDCA, which further activates the FXR receptor and regulates the TLR4-NF-κB signaling pathway. Our results confirm that Rh4 has the potential to be used as a modulator of gut microbiota for preventing and treatment of CRC.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: J Adv Res Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: J Adv Res Ano de publicação: 2024 Tipo de documento: Article