Background and Purpose: Acute pancreatitis (AP) is a painful and distressing disorder of the exocrine pancreas with no specific treatment. Diosgenyl saponins extracted from from Dioscorea zingiberensis C. H. Wright have been reported to protect against experimental models of AP. Diosgenin, or its derivatives are anti‐inflammatory in various conditions. However, the effects of diosgenin and its spiroacetal ring opened analogue, dihydrodiosgenin (Dydio), on AP have not been determined.Experimental Approach: Effects of diosgenin and Dydio on sodium taurocholate hydrate (Tauro)‐induced necrosis were tested, using freshly isolated murine pancreatic acinar cells. Effects of Dydio on mitochondrial dysfunction in response to Tauro, cholecystokinin‐8 and palmitoleic acid ethyl ester were also assessed. Dydio (5 or 10 mg·kg^‐1) was administered after the induction in vivo of Tauro‐induced AP (Wistar rats), caerulein‐induced AP and palmitoleic acid plus ethanol‐induced AP (Balb/c mice). Pancreatitis was assessed biochemically and histologically. Activation of pancreatic PI3Kγ/Akt was measured by immunoblotting.Key Results: Dydio inhibited Tauro‐induced activation of the necrotic cell death pathway and prevented pancreatitis stimuli‐induced mitochondrial dysfunction. Therapeutic administration of Dydio ameliorated biochemical and histopathological responses in all three models of AP through pancreatic mitochondrial protection and PI3Kγ/Akt inactivation. Moreover, Dydio improved pancreatitis‐associated acute lung injury through preventing excessive inflammatory responses.Conclusion and Implications: These data provide in vitro and in vivo mechanistic evidence that the diosgenin analogue, Dydio could be potential treatment for AP. Further medicinal optimization of diosgenin and its analogue might be a useful strategy for identifying lead candidates for inflammatory diseases.

Acute organ injuries represent a major public health concern, driven by inflammation and mitochondrial dysfunction, leading to cell damage and organ failure. In this study, we engineered neutrophil membrane–fused mitochondria (nMITO), which combine the injury-targeting and anti-inflammatory properties of neutrophil membrane proteins with the cell repairing function of mitochondria. nMITO effectively blocked inflammatory cascades and restored mitochondrial function, targeting both key mechanisms in acute organ injuries. In addition, nMITO selectively targeted damaged endothelial cells via β-integrins and were delivered to injured tissues through tunneling nanotubes, enhancing their regulatory effects on inflammation and cell damage. In mouse models of acute myocardial injury, liver injury, and pancreatitis, nMITO notably reduced inflammatory responses and repaired tissue damage. These findings suggest that nMITO is a promising therapeutic strategy for managing acute organ injuries.

Pancreatic cancer is one of the most aggressive tumors and also has a low survival rate. The dried spines of Gleditsia sinensis Lam are known as “Gleditsiae Spina” and they mostly contain flavonoids, phenolic acids, terpenoids, steroids, and other chemical components. In this study, the potential active components and molecular mechanisms of Gleditsiae Spina for treating pancreatic cancer were systematically revealed by network pharmacology, molecular docking and molecular dynamics simulations (MDs). RAC-alpha serine/threonine-protein kinase (AKT1), cellular tumor antigen p53 (TP53), tumor necrosis factor α (TNFα), interleukin-6 (IL6) and vascular endothelial growth factor A (VEGFA) were common targets of Gleditsiae Spina, human cytomegalovirus infection signaling pathway, AGE-RAGE signaling pathway in diabetic complications, and MAPK signaling pathway were critical pathways of fisetin, eriodyctiol, kaempferol and quercetin in the treatment of pancreatic cancer. Molecular dynamics simulations (MDs) results showed that eriodyctiol and kaempferol have long-term stable hydrogen bonds and high binding free energy for TP53 (−23.64 ± 0.03 kcal mol⁻¹ and −30.54 ± 0.02 kcal mol⁻¹, respectively). Collectively, our findings identify active components and potential targets in Gleditsiae Spina for the treatment of pancreatic cancer, which may help to explore leading compounds and potential drugs for pancreatic cancer.