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

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.

Saikosaponin D attenuates inflammatory response and cell apoptosis of lipopolysaccharide‐induced lung epithelial cells

“…Previous evidence has illustrated that SSD attenuates renal cell apoptosis in septic mice 13 . SSD suppresses acinar cell apoptosis by inactivating MAPK signaling pathway, thereby ameliorating pancreatic injury 24 . These reports support our findings in this study.…”

5-FU-miR-15a Inhibits Activation of Pancreatic Stellate Cells by Reducing YAP1 and BCL-2 Levels In Vitro

“…Furthermore, recent studies showed that multiple miRs (miR-301, miR-200c, miR-149, miR-139, miR-34b) can affect the activity of PSCs during chronic pancreatitis, and modulation of their levels leads to PSCs apoptosis [ 70 , 71 , 72 , 73 , 74 ]. Moreover, studies demonstrated that targeting PSCs with antifibrotic or anti-inflammatory compounds in a form of siRNA or small molecules could prevent chronic pancreatitis progression [ 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 ]. YAP1 has been shown to induce the activity of PSCs and stimulate pancreatic fibrosis during chronic pancreatitis [ 83 ].…”

Arecae pericarpium water extract alleviates chronic pancreatitis by deactivating pancreatic stellate cells

“…According to a recent study, it was confirmed that the size of pancreas in CP patients decreased by nearly 20%, and in particular, the incidence of apoptosis in acinar cells increased by 10 times compared to that in the normal group ( Schrader et al, 2009 ). It has also been reported that the histological and inflammatory score of CP worsens as the expression of factors that cause apoptosis of acinar cells increases ( Singh et al, 2008 ; Li et al, 2021 ). Therefore, the inhibitory effect of glandular destruction is considered an important factor in improving CP.…”