Qingre Xingyu recipe exerts inhibiting effects on ulcerative colitis development by inhibiting TNFα/NLRP3/Caspase-1/IL-1β pathway and macrophage M1 polarization

Liqin Ning; Ningyuan Ye; Bai Ye; Zhiwei Miao; Tingting Cao; Weimin Lu; Danhua Xu; Chang Tan; Yi Xu; Jing Yan

doi:10.1038/s41420-023-01361-w

Qingre Xingyu recipe exerts inhibiting effects on ulcerative colitis development by inhibiting TNFα/NLRP3/Caspase-1/IL-1β pathway and macrophage M1 polarization

Cell Death Discov. 2023 Mar 8;9(1):84. doi: 10.1038/s41420-023-01361-w.

Authors

Liqin Ning^#¹, Ningyuan Ye^#², Bai Ye³, Zhiwei Miao⁴, Tingting Cao³, Weimin Lu⁵, Danhua Xu¹, Chang Tan¹, Yi Xu⁶, Jing Yan⁷

Affiliations

¹ Chinese Medicine Master Studio, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210029, P. R. China.
² First Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, 210023, P. R. China.
³ Department of Gastroenterology, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210029, P. R. China.
⁴ Department of Gastroenterology, Zhangjiagang TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Suzhou, 215600, P. R. China.
⁵ Department of Internal Medicine, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210029, P. R. China.
⁶ Department of Gastroenterology, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210029, P. R. China. xuyi_jshtcm@outlook.com.
⁷ Key Laboratory for Metabolic Diseases in Chinese Medicine, First Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, 210023, P. R. China. yanjing@njucm.edu.cn.

^# Contributed equally.

Abstract

As a chronic inflammatory bowel disease, ulcerative colitis (UC) imposes a significant burden on public healthcare worldwide due to its increasing morbidity. Chinese medicines are regarded as potent therapeutic agents for UC treatment with minimal side effects. In the present study, we sought to determine the novel role of a traditional medicine Qingre Xingyu (QRXY) recipe in the development of UC and aimed to contribute to the currently available knowledge about UC by exploring the downstream mechanism of QRXY recipe in UC. Mouse models of UC were established by injections with dextran sulphate sodium (DSS), where the expression of tumor necrosis factor-alpha (TNFα), NLR family pyrin domain containing 3 (NLRP3), and interleukin-1β (IL-1β) was determined followed by an analysis of their interactions. The DSS-treated NLRP3 knockout (^-/-) Caco-2 cell model was successfully constructed. The in vitro and in vivo effects of the QRXY recipe on UC were investigated with the determination of disease activity index (DAI), histopathological scores, transepithelial electrical resistance, FITC-dextran, as well as cell proliferation and apoptosis. In vivo and in vitro experiments indicated that the QRXY recipe reduced the degree of intestinal mucosal injury of UC mice and functional damage of DSS-induced Caco-2 cells by inhibition of the TNFα/NLRP3/caspase-1/IL-1β pathway and M1 polarization of macrophages, and TNFα overexpression or NLRP3 knockdown could counterweigh the therapeutic effects of QRXY recipe. To conclude, our study elicited that QRXY inhibited the expression of TNFα and inactivated the NLRP3/Caspase-1/IL-1β pathway, thereby alleviating intestinal mucosal injury and relieving UC in mice.