Saikosaponin D Attenuates Pancreatic Injury Through Suppressing the Apoptosis of Acinar Cell via Modulation of the MAPK Signaling Pathway.

Caixia Li,Lei Yang,Lihua Cui,Jialin Cui,Naiqiang Cui,Shukun Zhang,Yuzhen Zhuo,Lanqiu Zhang

doi:10.3389/fphar.2021.735079

Abstract

Chronic pancreatitis (CP) is a progressive fibro-inflammatory syndrome. The damage of acinar cells is the main cause of inflammation and the activation of pancreatic stellate cells (PSCs), which can thereby possibly further aggravate the apoptosis of more acinar cells. Saikosaponind (SSd), a major active ingredient derived from Chinese medicinal herb bupleurum falcatum, which exerted multiple pharmacological effects. However, it is not clear whether SSd protects pancreatic injury of CP via regulating the apoptosis of pancreatic acinar cells. This study systematically investigated the effect of SSd on pancreatic injury of CP in vivo and in vitro. The results revealed that SSd attenuate pancreatic damage, decrease the apoptosis and suppress the phosphorylation level of MAPK family proteins (JNK1/2, ERK1/2, and p38 MAPK) significantly in the pancreas of CP rats. In addition, SSd markedly reduced the apoptosis and inflammation of pancreatic acinar AR42J cells induced by cerulein, a drug induced CP, or Conditioned Medium from PSCs (PSCs-CM) or the combination of PSCs-CM and cerulein. Moreover, SSd significantly inhibited the activated phosphorylation of JNK1/2, ERK1/2, and p38 MAPK induced by cerulein or the combination of PSCs-CM and cerulein in AR42J cells. Furthermore, SSd treatment markedly decreased the protein levels of p-JNK and p-p38 MAPK caused by PSCs-CM alone. In conclusion, SSd ameliorated pancreatic injury, suppressed AR42J inflammation and apoptosis induced by cerulein, interrupted the effect of PSCs-CM on AR42J cells inflammation and apoptosis, possibly through MAPK pathway.

Highlights

Pancreatitis is an inflammatory disease of the pancreas and divided into acute and chronic pancreatitis
The results revealed that SSd attenuate pancreatic damage, decrease the apoptosis and suppress the phosphorylation level of MAPK family proteins (JNK1/2, ERK1/2, and p38 MAPK) significantly in the pancreas of Chronic pancreatitis (CP) rats
The in vitro studies have shown that SSd attenuated the apoptosis of AR42J induced by cerulein or pancreatic stellate cells (PSCs)-CM or the combination of PSCs-CM and cerulein through significantly inhibited the activated phosphorylation of JNK1/2 and p38 MAPK

Summary

Introduction

Pancreatitis is an inflammatory disease of the pancreas and divided into acute and chronic pancreatitis. SSd Attenuates CP Pancreatic Injury resulting in the activation of pancreatic stellate cells (PSCs); fibrosis (Beyer et al, 2020). Previous studies on CP focuses on pancreatic stellate cells (PSCs), which majorly involved in the process of fibrosis. Acinar cell injury is the central to AP. The acinar cell injury involves acinar cell release of inflammatory mediators, activation of PSCs and recruitment of various immune cells (Patel Fine., 2005). The activated PSCs produce excessive extracellular matrix (ECM), manifested as pancreatic fibrosis (Chen et al, 2012; Erkan et al, 2012). The activated PSCs secret kinds of cytokines and chemokines that further facilitate the apoptosis of acinar cells (Xia et al, 2018). Preventing or suppressing the injury of acinar cells might be an efficacious therapeutic strategy for CP

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