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.

腺泡细胞坏死是急性胰腺炎（AP）最突出的病理生理变化之一。积雪草苷（AS）是一种三萜类化合物，具有证实的细胞凋亡和坏死相关活性。但是，还没有确定AS对AP的特定影响。在这项研究中，我们旨在使用两种小鼠模型研究AS对AP的保护作用。在青霉素诱导的轻度急性胰腺炎（MAP）模型中，我们发现AS给药以剂量依赖的方式降低了血清淀粉酶水平并减轻了胰腺组织的组织病理学表现。给予AS后，胰腺组织的Toll样受体4（TLR4）和坏死相关蛋白（RIP3和p-MLKL）含量降低。此外，TLR4缺乏消除了AS对小鼠油青素诱导的AP的保护作用。相应地，我们阐明了AS的体外作用，发现AS保护了胰腺腺泡细胞坏死，而TAK-242抵消了这种保护作用。同时，我们发现AS改善了由ICP诱导的重症急性胰腺炎模型中胰腺组织损伤和胰腺炎相关肺损伤的严重程度l-精氨酸。此外，分子对接结果揭示了AS和TLR4之间的相互作用。两者合计，我们的数据首次证实了AS通过TLR4途径对小鼠AP的保护作用。