Effect of Vulgarin and Epivulgarin on Ischemia-Reperfusion-Induced Pancreatic Injury in Rats: A Biochemical, Molecular, and Histopathological Evaluation

  • J Exp Pharmacol. 2026 Feb 2:18:563840. doi: 10.2147/JEP.S563840.
Hassan N Althurwi  1 ,  Rehab F Abdel-Rahman  2 ,  Tariq M Aljarba  3 ,  Hanan A Ogaly  4 ,  Saleh I Alqasoumi  5 ,  Ahmed I Foudah  3 ,  Maged S Abdel-Kader  3 ,  Gamal A Soliman  1
Affiliations
  • 1. Department of Pharmacology and Toxicology, College of Pharmacy, Prince Sattam bin Abdulaziz University, Al-Kharj, Saudi Arabia.
  • 2. Department of Pharmacology, National Research Centre, Giza, Egypt.
  • 3. Department of Pharmacognosy, College of Pharmacy, Prince Sattam bin Abdulaziz University, Al-Kharj, Saudi Arabia.
  • 4. Department of Biochemistry, College of Veterinary Medicine, Cairo University, Giza, Egypt.
  • 5. Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
PMID: 41878226 DOI: 10.2147/JEP.S563840
Abstract

Introduction: Ischemia/reperfusion (I/R) injury is a critical complication associated with pancreatic surgery, and transplantation, which frequently develops into acute pancreatitis due to increased oxidative stress and inflammatory cascades.

Aim: This study aimed to assess the protective effects of vulgarin (VLG) and epivulgarin (EPV) against pancreatic I/R- injury in rats.

Methods: Rats were given oral dosages of 10 or 20 mg/kg of VLG or EPV for two days prior to I/R and 24 h after reperfusion. Pancreatic I/R was induced by occluding the pancreatic blood supply for 60 minutes followed by reperfusion. Key biochemical markers including serum amylase, Lipase, tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β), malondialdehyde (MDA), and Glutathione Peroxidase (GPx) were measured. Additionally, pancreatic tissue expression of high mobility group box 1 (HMGB1) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) was assessed via immunohistochemistry.

Results: Pancreatic I/R significantly elevated serum levels of amylase (4.5-fold) and Lipase (5.8-fold), oxidative stress marker; MDA (8.5-fold), as well as pro-inflammatory cytokines; TNF-α (10.4-fold) and IL-1β (5.6-fold) compared to controls (p≤0.01). The antioxidant GPx activity was suppressed by 84% (p≤0.05). Treatment with VLG and EPV dose-dependently attenuated these changes, with the highest dose of EPV reducing serum amylase by 72% and MDA by 76% compared to untreated I/R rats (p≤0.01). Immunohistochemical analysis revealed marked downregulation of HMGB1 and NF-κB expression in VLG and EPV-treated groups. High-dose therapies showed near normalization of numerous biochemical and molecular parameters.

Conclusion: Vulgarin and epivulgarin exhibited significant protective effects against pancreatic I/R injury by reducing oxidative stress and suppressing HMGB1/NF-κB-mediated inflammatory signaling. These findings suggest the therapeutic potential of VLG and EPV in managing acute pancreatitis and related pancreatic injuries.

Keywords
HMGB1/NF-κB pathway; epivulgarin; pancreatic injury; rats; splenic artery occlusion; vulgarin.
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