Astragalus polysaccharide prevents ferroptosis in a murine model of experimental colitis and human Caco-2 cells via inhibiting NRF2/HO-1 pathway

Yanjun Chen; Jiayu Wang; Juntao Li; Jinghan Zhu; Ruoqin Wang; Qinhua Xi; Hongya Wu; Tongguo Shi; Weichang Chen

doi:10.1016/j.ejphar.2021.174518

Astragalus polysaccharide prevents ferroptosis in a murine model of experimental colitis and human Caco-2 cells via inhibiting NRF2/HO-1 pathway

Eur J Pharmacol. 2021 Nov 15:911:174518. doi: 10.1016/j.ejphar.2021.174518. Epub 2021 Sep 23.

Authors

Yanjun Chen¹, Jiayu Wang¹, Juntao Li², Jinghan Zhu², Ruoqin Wang², Qinhua Xi³, Hongya Wu⁴, Tongguo Shi⁵, Weichang Chen⁶

Affiliations

¹ Jiangsu Institute of Clinical Immunology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215000, China; Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215000, China; Suzhou Key Laboratory for Tumor Immunology of Digestive Tract, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215000, China.
² Jiangsu Institute of Clinical Immunology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215000, China; Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215000, China.
³ Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215000, China.
⁴ Jiangsu Institute of Clinical Immunology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215000, China; Suzhou Key Laboratory for Tumor Immunology of Digestive Tract, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215000, China; Jiangsu Key Laboratory of Clinical Immunology, Soochow University, Suzhou, Jiangsu, 215000, China.
⁵ Jiangsu Institute of Clinical Immunology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215000, China; Suzhou Key Laboratory for Tumor Immunology of Digestive Tract, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215000, China; Jiangsu Key Laboratory of Clinical Immunology, Soochow University, Suzhou, Jiangsu, 215000, China; Jiangsu Key Laboratory of Gastrointestinal Tumor Immunology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215000, China. Electronic address: shitg@suda.edu.cn.
⁶ Jiangsu Institute of Clinical Immunology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215000, China; Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215000, China; Suzhou Key Laboratory for Tumor Immunology of Digestive Tract, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215000, China. Electronic address: weichangchen@126.com.

PMID: 34562468
DOI: 10.1016/j.ejphar.2021.174518

Abstract

Ulcerative colitis (UC) is a relapsing and remitting inflammatory bowel disease (IBD), but current conventional drugs lack efficacy. Astragalus polysaccharide (APS) is an active ingredient of Astragalus membranaceus and has been shown to ameliorate experimental colitis. In the present study, we aimed to investigate how APS affects the ferroptosis of intestinal epithelial cells in dextran sulfate sodium (DSS)-induced experimental colitis in mice. Our data showed that APS administration attenuated total weight loss, colon length shortening, disease activity index (DAI) scores, histological damage, and the expression of inflammatory cytokines in the colon of DSS-challenged mice. Moreover, we observed that treatment with APS obviously inhibited ferroptosis in both DSS-challenged mice and RSL3-stimulated Caco-2 cells, as indicated by the decrease in the expression of ferroptosis-associated genes (PTGS2, FTH, and FTL) and the levels of surrogate ferroptosis markers (MDA, GSH, and iron load). Mechanistically, the inhibitory effects of APS on ferroptosis in DSS-challenged mice and RSL3-stimulated Caco-2 cells were associated with the NRF2/HO-1 pathway. Collectively, our findings identify a new role of APS in preventing ferroptosis in a murine model of experimental colitis and human Caco-2 cells via inhibiting NRF2/HO-1 pathway.

Keywords: Astragalus polysaccharide; Ferroptosis; Inflammation; NRF2; Ulcerative colitis.

MeSH terms

NF-E2-Related Factor 2*

Substances

NF-E2-Related Factor 2