Role and mechanism of caffeic acid in a mouse model of severe acute pancreatitis

Siyu XU; Tao LIU; Lulu LAN; Yining XUE; Wei WEI; Yi HAN; Sucheng MU; Haiyan SONG; Shilin DU

doi:10.12449/JCH250418

Volume 41 Issue 4

Apr. 2025

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Role and mechanism of caffeic acid in a mouse model of severe acute pancreatitis

DOI: 10.12449/JCH250418

Siyu XU¹,
Tao LIU¹,
Lulu LAN^{2, 3},
Yining XUE¹,
Wei WEI⁴,
Yi HAN⁴,
Sucheng MU⁴,
Haiyan SONG^{1
,
,
,},
Shilin DU^{2, 3
,
,
,}

1.
Institute of Digestive Diseases，Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine，Shanghai 200032，China
2.
Department of Emergency，Shanghai Geriatric Medical Center，Shanghai 201104，China
3.
Department of Emergency，Minhang Meilong Branch of Zhongshan Hospital，Fudan University，Shanghai 201104，China
4.
Department of Emergency，Zhongshan Hospital，Fudan University，Shanghai 200032，China

Research funding:

Clinical Research Special Project of Shanghai Municipal Health Commission (202040223)

More Information

Corresponding author: SONG Haiyan， songhy@126.com （ORCID： 0000-0003-2155-8110）; DU Shilin， du.shilin@zs-hospital.sh.cn （ORCID： 0009-0009-1640-0870）
Received Date: 2024-08-23
Accepted Date: 2024-11-13
Published Date: 2025-04-25

Abstract

Abstract

Objective To investigate the effect and potential mechanism of caffeic acid （CA） on severe acute pancreatitis （SAP） induced by caerulein combined with lipopolysaccharide （LPS）， and to provide a basis for the research on novel drugs for the treatment of SAP. Methods C57BL/6J mice， aged 6 weeks， were divided into control group， model group， CA group， and octreotide acetate （OA） group， with 6 mice in each group. The mice in the control group were given injection of normal saline， and those in the other groups were given intraperitoneal injection of caerulein combined with LPS to establish a mouse model of SAP. At 1 hour after the first injection of caerulein， the mice in the CA group and the OA group were given intraperitoneal injection of CA or subcutaneous injection of OA at an interval of 8 hours. The general status of the mice was observed after 24 hours of modeling， and serum， pancreas， lung， and colon samples were collected. HE staining was used to observe the histopathological changes of the pancreas and lungs， and the serum levels of α-amylase， lipase， tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， alanine aminotransferase， aspartate aminotransferase， and creatinine were measured. RT-PCR was used to measure the expression of proinflammatory factors in the pancreas and lungs； myeloperoxidase （MPO） immunohistochemistry was used to observe the degree of neutrophil infiltration； Western blot was used to measure the activation of nuclear factor-kappa B （NF-κB） and the level of citrullinated histone H3 （CitH3）， a marker for the formation of neutrophil extracellular traps （NETs）， in the pancreas and lungs， as well as the expression level of ZO-1 in colon tissue. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the Dunnett’s t-test was used for further comparison between two groups. Results Compared with the control group， the model group had severe injury in the pancreas and lungs and significant increases in the activity of serum α- amylase and lipase and the levels of the proinflammatory cytokines IL-6， interleukin-1β （IL-1β）， and TNF-α in serum and lung tissue （all P<0.05）， as well as significant increases in NF-κB activation， neutrophil infiltration， and the formation of NETs in the pancreas and lungs （all P<0.05）. Compared with the model group， the CA group had alleviated pathological injury of the pancreas and lungs and significant reductions in the activity of serum α-amylase and the levels of the proinflammatory cytokines IL-6， IL-1β， and TNF-α in serum and lung tissue （all P<0.05）， as well as significant reductions in NF-κB activation， neutrophil infiltration， and the formation of NETs in the pancreas and lungs （all P<0.05）. Conclusion CA can alleviate SAP induced by caerulein combined with LPS in mice， possibly by inhibiting neutrophil recruitment and the formation of NETs.
- Pancreatitis,
- Mice， Inbred C57BL,
- Caffeic Acid,
- Models， Animal

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References(42)

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Role and mechanism of caffeic acid in a mouse model of severe acute pancreatitis

DOI: 10.12449/JCH250418

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Role and mechanism of caffeic acid in a mouse model of severe acute pancreatitis

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