Escin Sodium Improves the Prognosis of Acute Pancreatitis via Promoting Cell Apoptosis by Suppression of the ERK/STAT3 Signaling Pathway.

Qian Zhang,Kai Sun,Chen Zhao,Lei Ren,Lei Zhang,Nan Zhang,Hu Tian,Haimei Wang,Linlin Yu,Ju Liu,Chengyu Chen,Xianming Wang,Ana Lloret

doi:10.1155/2021/9921839

Abstract

Acute pancreatitis (AP), an inflammatory disorder of the pancreas, can cause systemic inflammatory responses. Escin Sodium (ES), a natural mixture of triterpene saponins extracted from the dry ripe fruit of Fructus Aesculi or horse chestnut crude, has been demonstrated to have antiedematous, anti-inflammatory, and antiexudative effects. We here aim to investigate the effects of ES pretreatment on AP in vivo and in vitro and explore its potential molecular mechanism. In the present study, we demonstrated that ES pretreatment could apparently decrease amylase and lipase, downregulate inflammatory cytokines, and attenuate pancreatic damage. Additionally, the increased expression of apoptotic-related proteins and the results of flow cytometry demonstrated the effects of ES on promoting apoptosis in acinar cells. Moreover, ES could enhance mitochondrial membrane potential (MMP, ΔΨm) and reactive oxygen species (ROS) level and reduce intracellular calcium concentration, which are closely related to mitochondrial-mediated death. The effect of ES pretreatment on acinar cell apoptosis was furtherly confirmed by the regulatory pathway of the ERK/STAT3 axis. These results suggest that ES attenuates the severity of AP by enhancing cell apoptosis via suppressing the ERK/STAT3 signaling pathway. These findings provide evidence for ES which is treated as a novel and potent therapeutic for the treatment of AP.

Highlights

Acute pancreatitis (AP)—an inflammatory disorder of the pancreas—is the leading cause of admission to hospital for gastrointestinal disorders in many countries [1] and has become an economic burden to patients and health care system [2]
We furtherly explored the underlying mechanisms and acquired the results indicating that Escin Sodium (ES) promotes apoptosis in STC-induced acute pancreatitis via downregulating the ERK/STAT3 signaling pathway
All the above results indicated that the ES pretreatment had protection effects in acute pancreatitis induced by STC, and we explored whether it was related to promoting apoptosis subsequently

Summary

Introduction

Acute pancreatitis (AP)—an inflammatory disorder of the pancreas—is the leading cause of admission to hospital for gastrointestinal disorders in many countries [1] and has become an economic burden to patients and health care system [2]. SAP is characterized by persistent organ failure that results in multiple organ dysfunction syndrome (MODS) and systemic inflammatory response syndrome (SIRS) by activation of cytokine cascades during the early phase [4,5,6,7]. Patients who develop MODS or SIRS within the first few days are suffering from the increased risk of death, with mortality reported to be as great as 36– 50% [4, 5, 7]. The pathogenesis of AP is complicated and has not been elucidated completely yet

Results

Discussion

Conclusion