title: 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.
authors: Laboratory of Ethnopharmacology, Regenerative Medicine Research Center, West China Hospital/West China Medical School, Sichuan University, Chengdu, China.
authors: Rui
authors: R
authors: Zhang
authors: Department of Pediatric Gastroenterology, Children's Hospital of Pittsburgh of UPMC and School of Medicine, University of Pittsburgh, Pittsburgh, PA, United States.|Department of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
authors: Li
authors: L
authors: Wen
authors: Laboratory of Ethnopharmacology, Regenerative Medicine Research Center, West China Hospital/West China Medical School, Sichuan University, Chengdu, China.
authors: Yan
authors: Y
authors: Shen
authors: Department of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
authors: Na
authors: N
authors: Shi
authors: Laboratory of Ethnopharmacology, Regenerative Medicine Research Center, West China Hospital/West China Medical School, Sichuan University, Chengdu, China.
authors: Zhihua
authors: Z
authors: Xing
authors: Department of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
authors: Qing
authors: Q
authors: Xia
authors: Laboratory of Ethnopharmacology, Regenerative Medicine Research Center, West China Hospital/West China Medical School, Sichuan University, Chengdu, China.|College of Mathematics, Sichuan University, Chengdu, Sichuan, China.
authors: Hai
authors: H
authors: Niu
authors: Laboratory of Ethnopharmacology, Regenerative Medicine Research Center, West China Hospital/West China Medical School, Sichuan University, Chengdu, China.
authors: Wen
authors: W
authors: Huang
mesh_terms: D000818:Animals; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D027742:Dioscorea / Q000737:chemistry*; D004195:Disease Models, Animal; D005765:Gastrointestinal Agents / Q000008:administration & dosage / Q000302:isolation & purification* / Q000494:pharmacology*; D006651:Histocytochemistry; D008297:Male; D008807:Mice, Inbred BALB C; D008928:Mitochondria / Q000378:metabolism*; D019283:Pancreatitis, Acute Necrotizing / Q000473:pathology / Q000517:prevention & control*; D017208:Rats, Wistar; D012503:Saponins / Q000008:administration & dosage / Q000302:isolation & purification* / Q000494:pharmacology*; D016896:Treatment Outcome
chemical_list: D005765:Gastrointestinal Agents; D012503:Saponins