Using the Phillygenin Ameliorates the Severe Acute Pancreatitis in Rats by Inhibiting TLR4/NF-κB Pathway.

Background: There is no effective agent against the inflammation in severe acute pancreatitis (SAP). Phillygenin (PHI) exhibits potent anti-inflammatory activity. However, the molecular mechanisms underlying its effects on SAP remain unclear. The aim of the study was to explore the therapeutic effects and regulatory mechanism of PHI on SAP. Methods: Thirty male SD rats were randomly divided into control, SAP and PHI (30 mg/kg) treated groups. The effectiveness of the PHI treatment was determined by looking at the histological scores of the pancreas, the levels of serum amylase and lipase, pathological changes and myeloperoxidase (MPO) activity. The affinity between PHI and the TLR4/NF-κB proteins were predicted using molecular docking. Rat pancreatic AR42J cells were divided into control, cerulein plus LPS and PHI-treated groups (12.5, 25 and 50 μg/mL). In vivo and vitro experiments, the effect of PHI on the release of TNF-α, IL-6, and IL-1β were measured by ELISA. The Western blot and immunohistochemistry were used to uncover the underlying molecular mechanisms targeting on TLR4/NF-κB. Results: PHI treatment significantly improved pancreatic pathology ( Conclusion: PHI exhibits a protective effect against SAP. It can alleviate SAP in rats by inhibiting TLR4/NF-κB pathway. Therefore, PHI may be considered as a novel therapeutic agent against SAP.