Abstract
Acute pancreatitis (AP) is a painful inflammatory disorder of the exocrine pancreas, ranking as the most common gastrointestinal reasons for hospitalization with no specific therapy currently. Diosgenyl saponins extracted from natural products and diosgenin or its derivatives have been shown to exert anti-inflammatory effects in various diseases. However, the therapeutic effects of diosgenyl saponins from Dioscorea zingiberensis C. H. Wright in AP have not yet been determined. Five compounds were extracted and screened for taurocholate-induced necrosis in mouse pancreatic acinar cells. Particularly, 26-O-β-d-glucopyranosyl-3β, 22α, 26-trihydroxy-25(R)-furosta-5-en-3-O-[α-L-rhamnopyranosyl-(1 → 4)]-β-d-glucopyranoside (compound 1) exhibited the best protective effects with no toxicity observed. Next, we showed compound 1 concentration-dependently inhibited necrotic cell death pathway activation and 2.5 mM compound 1 also prevented the loss of mitochondrial membrane potential, adenosine triphosphate production, and reactive oxygen species generation in mouse pancreatic acinar cells. Finally, we showed compound 1 protected against three clinically representative murine models of AP and significantly improved pancreatitis-associated acute lung injury. These data provide in vitro and in vivo evidence that one compound of diosgenyl saponins can be potential treatment for AP. This study suggests natural saponins may serve as fruitful sources for exploring/identifying potential therapies for inflammatory diseases.
Highlights
Acute pancreatitis (AP) is a painful inflammatory disorder of the exocrine pancreas, ranking as the most common gastrointestinal reasons for hospitalization with no specific therapy currently
We screened cytoprotective effects of compounds 1–5, using a well-established necrosis assay to assess plasma membrane rupture staining with propidium iodide (PI) in mouse pancreatic acinar cells
We found five saponin compounds isolated from Dioscorea zingiberensis C
Summary
Acute pancreatitis (AP) is a painful inflammatory disorder of the exocrine pancreas, ranking as the most common gastrointestinal reasons for hospitalization with no specific therapy currently. We showed compound 1 protected against three clinically representative murine models of AP and significantly improved pancreatitis-associated acute lung injury These data provide in vitro and in vivo evidence that one compound of diosgenyl saponins can be potential treatment for AP. We further demonstrated that compound 1 concentration-dependently protected against necrotic cell death pathway activation with the maximal inhibitory effect at 2.5 mM and the same concentration (2.5 mM) prevented the loss of mitochondrial membrane potential (ΔΨm), ATP depletion and ROS production in mouse pancreatic acinar cells. Compound 1 significantly improved pancreatitis-associated acute lung injury (ALI), which is one of the most common complications of AP and associated with higher mortality[10,19] These data provide in vitro and in vivo evidence that diosgenyl saponins from Dioscorea zingiberensis C. Compound 1 can be potential treatment for AP
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