Asiaticoside ameliorates acinar cell necrosis in acute pancreatitis via toll-like receptor 4 pathway

Abstract

Acinar cell necrosis is one of the most prominent pathophysiological changes of acute pancreatitis (AP). Asiaticoside (AS) is a triterpene compound with confirmed apoptosis-and necrosis-related activities. However, the specific effects of AS on AP have not been determined. In this study, we aimed to investigate the protective effect of AS on AP using two mouse models. In the caerulein-induced mild acute pancreatitis (MAP) model, We found that AS administration reduced serum amylase levels and alleviated the histopathological manifestations of pancreatic tissue in a dose-dependent manner. And the levels of toll-like receptor 4 (TLR4) and necrotic related proteins (RIP3 and p-MLKL) of pancreatic tissue were reduced after AS administration. In addition, TLR4 deficiency eliminated the protective effect of AS on AP induced by caerulein in mice. Correspondingly, we elucidated the effect of AS in vitro and found that AS protected against pancreatic acinar cells necrosis and TAK-242 counteracted this protective effect. Meanwhile, we found that AS ameliorated the severity of pancreatic tissue injury and pancreatitis-associated lung injury in a severe acute pancreatitis model induced by l-arginine. Furthermore, Molecular docking results revealed interaction between AS and TLR4. Taken together, our data for the first time confirmed the protective effects of AS on AP in mice via TLR4 pathway.

Keywords: Acute pancreatitis; Asiaticoside; Necrosis; Pancreatic acinar cells; Toll-like receptor 4.