Abstract

Morin, a naturally occurring bioactive compound shows great potential as an antioxidant, anti-inflammatory agent, and regulator of blood glucose levels. However, its low water solubility, poor lipid solubility, limited bioavailability, and rapid clearance in vivo hinder its application in blood glucose regulation. To address these limitations, we report an enzymatically synthesized nanosized morin particle (MNs) encapsulated in sodium alginate microgels (M@SA). This approach significantly enhances morin's delivery efficiency and therapeutic efficacy in blood glucose regulation. Utilizing horseradish peroxidase, we synthesized MNs averaging 305.7 ± 88.7 nm in size. These MNs were then encapsulated via electrohydrodynamic microdroplet spraying to form M@SA microgels. In vivo studies revealed that M@SA microgels demonstrated prolonged intestinal retention and superior efficacy compared with unmodified morin and MNs alone. Moreover, MNs notably improved glucose uptake in HepG2 cells. Furthermore, M@SA microgels effectively regulated blood glucose, lipid profiles, and oxidative stress in diabetic mice while mitigating liver, kidney, and pancreatic damage and enhancing anti-inflammatory responses. Our findings propose a promising strategy for the oral administration of natural compounds for blood glucose regulation, with implications for broader therapeutic applications.

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