Emodin enhances the therapeutic efficacy of human umbilical cord mesenchymal stem cell-derived extracellular vesicles in acute pancreatitis-induced lung injury.

Acute pancreatitis (AP) frequently leads to acute lung injury, a major contributor to AP-related mortality. Emodin, a natural anti-inflammatory compound, shows therapeutic promise. Human umbilical cord mesenchymal stem cell-derived extracellular vesicles (hUC-MSC-EVs) also exhibit intrinsic therapeutic properties against AP-associated lung injury. This study investigated whether encapsulating emodin into these EVs (EVs-Emodin) enhances their protective effects in alleviating lung injury caused by AP-triggered systemic inflammation.EVs-Emodin were encapsulated into hUC-MSC-EVs and compared with free emodin in vitro using TNF-α-treated BEAS-2B lung epithelial cells and in vivo using a sodium taurocholate (STC)-induced AP mouse model. Cell viability, apoptosis, ROS production, inflammatory cytokine release, mitochondrial morphology, and pyroptosis markers were assessed using CCK-8, flow cytometry, ELISA, qPCR, transmission electron microscopy, Western blotting, and immunostaining.EVs-Emodin exhibited effective uptake and significantly improved BEAS-2B cell viability compared to emodin or hUC-MSC-EVs alone. They also more effectively reduced TNF-α-induced apoptosis, ROS accumulation, inflammatory cytokine production, and pyroptotic signaling. In AP mice, EVs-Emodin administration is more efficient in preserving lung tissue structure, restoring lung epithelial proliferation, and reducing inflammation and pyroptosis.Encapsulation of emodin in hUC-MSC-EVs significantly enhances their therapeutic efficacy against AP-induced lung injury. EVs-Emodin represent a promising strategy for targeted treatment of inflammatory complications in AP.