One compound of saponins from Disocorea zingiberensis protected against experimental acute pancreatitis by preventing mitochondria-mediated necrosis

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.

Dihydrodiosgenin protects against experimental acute pancreatitis and associated lung injury through mitochondrial protection and PI3Kγ/Akt inhibition

“…Therefore, we hypothesized that Dydio could prevent excessive inflammatory responses and thus mitigate distant organ injury associated with pancreatitis. As ALI is one of the most frequent distant organ injuries associated with severe AP (Zhang et al, ), we then examined the effects of Dydio on ALI in our models of AP. Treatment with Dydio (5 and 10 mg·kg −1 ) significantly reduced lung MPO in all the models of AP (Tauro, CER and FAEE) (Figure A).…”

“…We have recently reported that diosgenyl saponins isolated from from Disocorea zingiberensis C. H. Wright, 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 ) protected against pancreatic acinar injury and three models of experimental AP (Zhang et al, ), providing the impetus to further isolate and identify the most potent compound of the diosgenyl saponins for protection against AP. However, extracting diosgenyl saponins from D. zingiberensis C. H. Wright or other natural sources is not ideal for medicinal chemistry modifications, as the process of isolation is time‐consuming and purification is challenging.…”

Phytochemicals with protective effects against acute pancreatitis: a review of recent literature

“…Moreover, it also significantly reduced histological pancreatic injury in mice (Zhang et al. 2016 ). Remarkably, the potential mechanism of this compound is still unclear, and much more research is still needed.…”