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

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.