Rutin protects the pancreas from inflammatory injury and oncogene-driven tumorigenesis by inhibiting acinar to ductal metaplasia

  • Eur J Pharmacol. 2025 Mar 20:998:177536. doi: 10.1016/j.ejphar.2025.177536.
Xueni Wang  1 ,  Mengyuan Gong  2 ,  Zeen Zhu  3 ,  Bo Zhang  4 ,  Liang Han  5 ,  Wei Li  6 ,  Zheng Wu  7 ,  Qingyong Ma  8 ,  Zheng Wang  9 ,  Weikun Qian  10
Affiliations
  • 1. Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, China; Pancreatic Disease Center of Xi'an Jiaotong University, Xi'an, 710061, China. Electronic address: [email protected].
  • 2. Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, China; Pancreatic Disease Center of Xi'an Jiaotong University, Xi'an, 710061, China. Electronic address: [email protected].
  • 3. Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, China; Pancreatic Disease Center of Xi'an Jiaotong University, Xi'an, 710061, China. Electronic address: [email protected].
  • 4. Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, China; Pancreatic Disease Center of Xi'an Jiaotong University, Xi'an, 710061, China. Electronic address: [email protected].
  • 5. Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, China; Pancreatic Disease Center of Xi'an Jiaotong University, Xi'an, 710061, China. Electronic address: [email protected].
  • 6. Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, China; Pancreatic Disease Center of Xi'an Jiaotong University, Xi'an, 710061, China. Electronic address: [email protected].
  • 7. Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, China; Pancreatic Disease Center of Xi'an Jiaotong University, Xi'an, 710061, China. Electronic address: [email protected].
  • 8. Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, China; Pancreatic Disease Center of Xi'an Jiaotong University, Xi'an, 710061, China. Electronic address: [email protected].
  • 9. Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, China; Pancreatic Disease Center of Xi'an Jiaotong University, Xi'an, 710061, China. Electronic address: [email protected].
  • 10. Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, China; Pancreatic Disease Center of Xi'an Jiaotong University, Xi'an, 710061, China. Electronic address: [email protected].
PMID: 40120793 DOI: 10.1016/j.ejphar.2025.177536
Abstract

Rutin is a valuable traditional Chinese medicine known for its anti-inflammatory and Anticancer effects. It has been shown to be effective in treating various inflammation-associated diseases. Here, we investigated the influence of rutin on acute pancreatitis and tumorigenesis. Using C57BL/6J mice and Kras mutant transgenic mice, we induced pancreatitis and acinar regeneration models. Pancreatic malondialdehyde (MDA), superoxide dismutase (SOD) activity and reduced glutathione (GSH) contents were measured for oxidative stress. Histological staining and a pancreatic acinar 3D culture model were used to clarify the influence of rutin on ADM in vivo and in vitro. Western blotting was adopted to detect ADM markers amylase and CK19. We found that rutin ameliorated inflammatory injury to the pancreas in both caerulein- and arginine-induced AP. Then, we revealed that the anti-damage effect of rutin may be due to its inhibition of oxidative stress. In addition, an acinar 3D culture model showed that rutin inhibited the formation of ADM by activating AMPK in acinar cells. Finally, the activation of AMPK is believed to be a potential mechanism by which rutin exerts inhibitory effects on Kras-driven tumorigenesis. Rutin inhibited AP-induced pancreatic injury and oncogenic Kras-driven tumorigenesis by inhibiting ADM.

Keywords
Acinar-to-ductal metaplasia; Acute pancreatitis; Rutin; Tumorigenesis.
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