Emodin-Enhanced hUC-MSC extracellular vesicles alleviate acute pancreatitis by targeting inflammation and pyroptosis.

BACKGROUND: Acute pancreatitis (AP) is a complex condition requiring immediate treatment. Both extracellular vesicles derived from human umbilical cord mesenchymal stem cells (hUC-MSC-EVs) and emodin, a naturally occurring anthraquinone used in traditional Chinese medicine, have shown therapeutic potential in treating AP. However, the mechanisms by which hUC-MSC-EVs and emodin alleviate AP, and whether they exert a synergistic effect on inflamed pancreatic tissues, remain unclear. OBJECTIVE: Our study aimed to evaluate the efficacy of emodin, hUC-MSC-EVs, and their combination in AP, explore synergistic mechanisms, and propose hUC-MSC-EVs as a novel drug delivery strategy for therapeutic applications. DESIGN: In this study, we developed AP cell, organoid, and animal models to compare the effects of emodin, hUC-MSC-EVs, and emodin-loaded hUC-MSC-EVs on cell viability, inflammation, and pyroptosis. RESULTS: Our data revealed that all three treatments improved cell viability, reduced pro-inflammatory cytokine expression, and inhibited pyroptosis in the AP models. Notably, the encapsulation of emodin significantly enhanced the protective effects of hUC-MSC-EVs.These findings suggest that emodin's protective effects on inflamed pancreatic tissues may be attributed, at least in part, to its anti-inflammatory and anti-pyroptotic properties. Additionally, our study proposes a novel strategy for engineering hUC-MSC-EVs for potential therapeutic applications in AP treatment.