2. Academic Validation
  3. Ginsenoside derivative AD-1 suppresses colitis-associated colorectal cancer progression by reprogramming tumor-associated macrophage polarization via the AMPK/mTOR-glycolysis pathway

Ginsenoside derivative AD-1 suppresses colitis-associated colorectal cancer progression by reprogramming tumor-associated macrophage polarization via the AMPK/mTOR-glycolysis pathway

  • Bioorg Chem. 2026 Feb:169:109458. doi: 10.1016/j.bioorg.2025.109458.
Yuan Fu 1,  Jinfang Zhang 1,  Xizhu Fang 2,  Yining An 1,  Shengnan Huang 1,  Xianmin Feng 3,  Xiaoming Jiang 4,  Zhihua Chen 5,  Xingguo Quan 2,  Dan Jin 6,  Yuqing Zhao 7,  Fangfang Li 8
Affiliations

Affiliations

  • 1 Immunology Biology Key Laboratory, Yanbian University, Yanji 133002, China; Key Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, Yanbian University, Yanji 133002, China; Department of Immunology and Pathogenic Biology, College of Medicine, Yanbian University, Yanji 133002, China.
  • 2 Immunology Biology Key Laboratory, Yanbian University, Yanji 133002, China; Department of Immunology and Pathogenic Biology, College of Medicine, Yanbian University, Yanji 133002, China.
  • 3 Jilin Provincial Key Laboratory of Changbai Mountain Authentic Medical Materias' Quality Assurance & Resources Development, Jilin 132013, China.
  • 4 Immunology Biology Key Laboratory, Yanbian University, Yanji 133002, China; Jilin Provincial Key Laboratory of Changbai Mountain Authentic Medical Materias' Quality Assurance & Resources Development, Jilin 132013, China.
  • 5 Immunology Biology Key Laboratory, Yanbian University, Yanji 133002, China; Key Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, Yanbian University, Yanji 133002, China; Department of Nursing Science, College of Nursing, Yanbian University, Yanji 133002, China.
  • 6 Immunology Biology Key Laboratory, Yanbian University, Yanji 133002, China; Key Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, Yanbian University, Yanji 133002, China; Department of Immunology and Pathogenic Biology, College of Medicine, Yanbian University, Yanji 133002, China. Electronic address: 0000002048@ybu.edu.cn.
  • 7 Key Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, Yanbian University, Yanji 133002, China. Electronic address: zyq2022@126.com.
  • 8 Immunology Biology Key Laboratory, Yanbian University, Yanji 133002, China; Department of Immunology and Pathogenic Biology, College of Medicine, Yanbian University, Yanji 133002, China. Electronic address: ffli@ybu.edu.cn.
PMID: 41483706 DOI: 10.1016/j.bioorg.2025.109458
Abstract

Persistent inflammation plays a pivotal role in the development of colorectal Cancer (CRC), and the incidence of colitis-associated colorectal Cancer (CAC) continues to rise. Thus, exploring treatment strategies for CAC is critical for the prevention and management of CRC. Natural products derived from traditional Chinese medicine have recently gained attention for their therapeutic potential in Cancer prevention. Here, we demonstrate that the ginsenoside derivative AD-1 significantly inhibits tumor progression in both AOM/DSS-induced CAC mice and CRC xenograft models. Moreover, AD-1 modulates tumor-associated macrophage (TAM) polarization both in vivo and in vitro. Specifically, AD-1 increases M1-like TAM polarization while suppressing M2 -like TAM in the spleens and colonic tissues of CAC mice, as well as in tumor tissues of CRC xenograft models. In vitro, AD-1 similarly promotes M1-like polarization and inhibits M2-like polarization in a TAM model established by co-culturing RAW264.7 cells with CT26 supernatant. Mechanistically, AD-1 activates AMPK signaling and inhibits mTOR activation, leading to enhanced glycolysis, which contributes to TAM metabolic reprogramming and polarization. Collectively, our study suggests that AD-1 represents a promising natural agent for modulating the tumor immune microenvironment and preventing the progression of inflammation-associated CRC.

Keywords

AMPK/mTOR signaling pathway; Colitis-associated colorectal cancer; Ginsenoside derivative AD-1; Glycolysis; Tumor-associated macrophage polarization.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z