L-Arginine-induced acute pancreatitis and its associated lung injury in rats: Down-regulation of TLR-4/MAPK-p38/JNK signaling pathway via Ginkgo biloba extract EGb 761

Objective(s): Acute pancreatitis (AP) is an abrupt inflammatory condition characterized by a storm of inflammatory cytokines leading to high morbidity and mortality. The current study aimed to examine the efficacy of Ginkgo biloba extract EGb 761 (GBE) in the treatment of L-arginine-induced AP and its associated lung injury. Materials and Methods: Forty rats were randomly assigned into four groups. The normal group received only saline intraperitoneally while the other groups received two intraperitoneal L-arginine injections (250 mg/100 g b.wt) separated by a 1 -hour interval to provoke AP. GBE (200 and 400 mg/ kg/day, PO) was administered for 2 weeks post -induction of pancreatitis. Sera and pancreatic tissues were isolated. Results: The outcome of the present study revealed that GBE ameliorated the elevated levels of serum amylase, lipase, and pancreatic inflammatory mediators viz., tumor necrosis factor -alpha (TNF- alpha), mitogen-activated protein kinase P38 (MAPK-P38), c -Jun N -terminal kinase 1 (JNK1), and nuclear factor -kappa B (NF -kappa B). Moreover, GBE restored the pancreatic gene expression of Toll -like receptor 4 (TLR4) and prostatic acid phosphatase-2 (PAP -2). Pancreatic and lung histopathological examinations confirmed the aforementioned parameters. Conclusion: GBE interfered with the mechanistic pathway of L-arginine-induced acute pancreatic and its associated lung injury. Due to its anti-inflammatory properties, GBE can be used as a novel therapeutic candidate for the treatment of AP through down -regulating TLR-4/MAPK-p38/JNK and MAPK- p38/NF-kappa B signaling cascades.