Panax notoginseng saponins prevent colitis-associated colorectal cancer via inhibition IDO1 mediated immune regulation

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-inf...

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Bibliographic Details
Published in:Chinese journal of natural medicines 2022-04, Vol.20 (4), p.258-269
Main Authors: LI, Xue-Ming, YUAN, Ding-Yi, LIU, Ya-Hui, ZHU, Lei, QIN, Hong-Kun, YANG, Yu-Bing, LI, Yan, YAN, Fang, WANG, Ya-Jing
Format: Article
Language:English
Subjects:
Animals
Chemoprevention
Colitis - complications
Colitis - drug therapy
Colitis-associated colorectal cancer
Colitis-Associated Neoplasms - drug therapy
Humans
IDO1
Macrophages
Mice
Panax notoginseng
Panax notoginseng saponins
Saponins - pharmacology
Saponins - therapeutic use
Treg cells
Tumor Microenvironment
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Summary: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.
ISSN:1875-5364
1875-5364
DOI:10.1016/S1875-5364(22)60179-1