Quercetin ameliorates ulcerative colitis by restoring the balance of M2/M1 and repairing the intestinal barrier via downregulating cGAS‒STING pathway

Fei Gao; Feng Zhu; Bo Shuai; Meng Wu; Chunzhu Wei; Yuyi Yuan; Yang Gui; Yushi Tian; Heng Fan; Hui Wu

doi:10.3389/fphar.2024.1351538

Quercetin ameliorates ulcerative colitis by restoring the balance of M2/M1 and repairing the intestinal barrier via downregulating cGAS‒STING pathway

Front Pharmacol. 2024 May 7:15:1351538. doi: 10.3389/fphar.2024.1351538. eCollection 2024.

Authors

Fei Gao^#¹, Feng Zhu^#¹, Bo Shuai^#¹, Meng Wu^#², Chunzhu Wei¹, Yuyi Yuan¹, Yang Gui¹, Yushi Tian¹, Heng Fan¹, Hui Wu¹

Affiliations

¹ Department of Integrated Traditional Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
² Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

^# Contributed equally.

Abstract

Macrophage polarization is closely associated with the pathogenesis of ulcerative colitis (UC). Quercetin, a flavonoid, has shown promise as a treatment for inflammatory diseases, but its specific mechanism of action remains unclear. This study investigates whether quercetin can regulate intestinal macrophage polarization and promote intestinal tissue repair via the cGAS-STING pathway for the treatment of UC. In vivo, mice with 3% DSS-induced UC were intraperitoneally injected with quercetin and RU.521 for 7 days, following which their general conditions and corresponding therapeutic effects were assessed. The impact of interferon-stimulated DNA (ISD) and quercetin on macrophage polarization and the cGAS-STING pathway was investigated using RAW264.7 cells and bone marrow-derived macrophages (BMDMs) in vitro. The results demonstrated that ISD induced M1 macrophage polarization and activated the cGAS-STING pathway in vitro, while quercetin reversed ISD's inflammatory effects. In vivo, quercetin suppressed the cGAS-STING pathway in the intestinal macrophages of DSS-induced UC mice, which reduced M1 macrophage polarization, increased M2 polarization, and facilitated intestinal barrier repair in UC. Taken together, these findings provide new insights into the mechanisms via which quercetin could be used to treat UC.

Keywords: immunity; intestinal barrier; macrophage polarization; quercetin; ulcerative colitis.

Grants and funding

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This work was supported by the National Natural Science Foundation of China (no. 82104637), and partially funded by the National Natural Science Foundation of China (no. 82174182).