Panax notoginseng saponins prevent colitis-associated colorectal cancer via inhibition IDO1 mediated immune regulation.
10.1016/S1875-5364(22)60179-1
- Author:
Xue-Ming LI
1
;
Ding-Yi YUAN
1
;
Ya-Hui LIU
2
;
Lei ZHU
1
;
Hong-Kun QIN
1
;
Yu-Bing YANG
1
;
Yan LI
3
;
Fang YAN
4
;
Ya-Jing WANG
5
Author Information
1. Department of physiology, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing 210009, China.
2. Department of Pharmaceutical Analysis, School of pharmacology, China Pharmaceutical University, Nanjing 210009, China.
3. Department of Chronic Communicable Disease, Jiangsu Provincial Center for Disease Prevention and Control, Nanjing 210009, China.
4. Department of Pharmaceutical Analysis, School of pharmacology, China Pharmaceutical University, Nanjing 210009, China. Electronic address: cpuyanfang@hotmail.com.
5. Department of physiology, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing 210009, China. Electronic address: cpuwyj@cpu.edu.cn.
- Publication Type:Journal Article
- Keywords:
Chemoprevention;
Colitis-associated colorectal cancer;
IDO1;
Panax notoginseng saponins;
Treg cells
- MeSH:
Animals;
Colitis/drug therapy*;
Colitis-Associated Neoplasms/drug therapy*;
Humans;
Macrophages;
Mice;
Panax notoginseng;
Saponins/therapeutic use*;
Tumor Microenvironment
- From:
Chinese Journal of Natural Medicines (English Ed.)
2022;20(4):258-269
- CountryChina
- Language:English
-
Abstract:
Colorectal cancer (CRC) is the third most lethal cancer and leading cause of cancer mortality worldwide. A key driver of CRC development is colon inflammatory responses especially in patients with inflammatory bowl disease (IBD). It has been proved that Panax notoginseng saponins (PNS) have anti-inflammatory, anti-oxidant and anti-tumor effects. The chemopreventive and immunomodulatory functions of PNS on colitis-associated colorectal cancer (CAC) have not been evaluated.This present study was designed to study the potential protective effects of PNS on AOM/DSS-induced CAC mice to explore the possible mechanism of PNS against CAC. Our study showed that PNS significantly alleviated colitis severity and prevented the occurrence of CAC. Functional assays revealed that PNS relieved immunosuppression of Treg cells in the CAC microenvironment by inhibiting the expression of IDO1 mediated directly by signal transducer and activator of transcription 1 (STAT1) rather than phosphorylated STAT1. Ultimately, Rh1, one of the PNS metabolites, exhibited the best inhibitory effect on IDO1 enzyme activity. Our study showed that PNS exerted significant chemopreventive function and immunomodulatory properties on CAC. It could reduce macrophages accumulation and Treg cells differentiation to reshape the immune microenvironment of CAC. These findings provided a promising approach for CAC intervention.
