Pristimerin ameliorates colitis‑induced intestinal mucosal injury by inhibiting intestinal epithelial necroptosis

Liu,Siqi; Wang,Yuanyuan; Lu,Keyi; Shi,Yifan; Wang,Zhibin; Xu,Erping

doi:10.3892/mmr.2025.13518

Pristimerin ameliorates colitis‑induced intestinal mucosal injury by inhibiting intestinal epithelial necroptosis

Authors:
- Siqi Liu
- Yuanyuan Wang
- Keyi Lu
- Yifan Shi
- Zhibin Wang
- Erping Xu
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Affiliations: Collaborative Innovation Center of Research and Development on The Whole Industry Chain of Yu‑Yao, Henan Province, Henan University of Chinese Medicine, Zhengzhou, Henan 450046, P.R. China, Collaborative Innovation Center of Research and Development on The Whole Industry Chain of Yu‑Yao, Henan Province, Henan University of Chinese Medicine, Zhengzhou, Henan 450046, P.R. China, Department of Critical Care Medicine, School of Anesthesiology, Naval Medical University, Shanghai 200433, P.R. China
Published online on: April 4, 2025 https://doi.org/10.3892/mmr.2025.13518
Article Number: 153
Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Ulcerative colitis (UC) is a non‑specific inflammatory bowel disease characterized by inflammation of the colonic and rectal mucosa and submucosa and has a globally increasing incidence. A compromised intestinal epithelial barrier function has been established as the primary etiological factor in UC, with necroptosis of intestinal epithelial cells exacerbating barrier disruption. Consequently, the inhibition of necroptosis in these cells has the potential to ameliorate colitis severity and preserve intestinal integrity, thereby offering a promising therapeutic approach for UC management. Pristimerin, a naturally occurring pentacyclic triterpenoid derived from Tripterygium wilfordii Hook.f., has been used in the treatment of various diseases. Although pristimerin has been documented to have therapeutic effects on UC, there is a lack of studies exploring its mechanism of action via necroptosis. The present study aimed to elucidate the role of pristimerin in the treatment of UC by examining its inhibitory effects on necroptosis through both in vivo and in vitro experimental approaches. Pristimerin was found to markedly enhance body weight, colon length and intestinal barrier function, while concurrently reducing fecal blood loss in murine models of colitis. Furthermore, both in vivo and in vitro, pristimerin effectively inhibited the phosphorylation of key necroptosis mediators, including receptor‑interacting protein kinase 1, receptor‑interacting protein kinase 3 and mixed lineage kinase domain‑like protein. These findings collectively suggested that the therapeutic effects of pristimerin in UC may be attributed, at least in part, to its ability to suppress necroptosis, thereby improving intestinal barrier integrity.

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