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Updated: Jan 14, 2026
Preparing a Mice Model of Severe Acute Pancreatitis via a Combination of Caerulein and Lipopolysaccharide Intraperitoneal Injection
Published on: May 10, 2024
Rutaecarpine targets F-box and WD repeat domain containing 11 to inhibit inflammatory infiltration and alleviate
Yan Jia1,2, Yu-Xin Shi1,2, Huan Gu1,2
1Department of Gastroenterology, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China.
Background:
The mortality rate for severe cases of acute pancreatitis (AP), a common gastrointestinal emergency, is as high as 30%. Our previous study has shown that rutaecarpine (Rut) has a therapeutic effect on AP.
Aim:
To investigate the role of F-box and WD repeat domain containing 11 (FBXW11) in AP models and to assess whether Rut mitigates AP by regulating FBXW11.
Methods:
AP rat model was established and treated with Rut, followed by biochemical analysis of serum amylase and lipase, hematoxylin and eosin staining of pancreatic tissue, and immunohistochemistry detection of pancreatic Ly6G, CD11b, and myeloperoxidase. Assay kits were used to detect oxidative stress-related indicators in pancreatic tissue and inflammatory factors in serum. AR42J cells were treated with cerulein to model AP and subjected to Cell Counting Kit-8 viability assay, flow cytometry apoptosis assay, and immunofluorescence detection of reactive oxygen species to elucidate the mechanistic involvement of the enhancer of zeste homolog 2 (EZH2)-FBXW11 axis in Rut-mediated protection against AP. The EZH2-histone H3 binding and H3 methylation were evaluated using co-immunoprecipitation.
Results:
Rut treatment ameliorated AP severity, as evidenced by reduced serum levels of pancreatic enzymes (amylase and lipase) and attenuated histological damage. Rut also decreased inflammatory markers (interleukin-1 beta, interleukin-6, and tumor necrosis factor alpha), tissue oxidative stress (malondialdehyde), and neutrophil infiltration (Ly6G, CD11b, and myeloperoxidase) levels in rats with AP. Moreover, Rut restored pancreatic antioxidant capacity (glutathione and superoxide dismutase). In vitro, Rut pre-incubation enhanced cell viability and suppressed cerulein-induced apoptosis and oxidative stress. Rut increased EZH2 expression while decreasing FBXW11 expression. FBXW11 overexpression eliminated the protective effect of Rut against AP. Further analysis revealed that EZH2 binds to H3 and upregulates H3 methylation levels, thereby inhibiting FBXW11 expression.
Conclusion:
Collectively, our findings demonstrate that Rut ameliorates AP by upregulating EZH2, thereby enhancing H3 methylation and suppressing FBXW11 expression.
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