Abstract: The urgent need for diabetes prevention and treatment, coupled with the side effects associated with long-term use of existing hypoglycemic drugs, has spurred significant interest in developing natural, highly effective, and low-toxicity active ingredients. Although quercetin and kaempferol exhibit hypoglycemic potential, their application is limited by poor water solubility, low stability, and insufficient bioavailability. To address this, this study utilized food-grade corn gluten protein and gum arabic to construct a quercetin-kaempferol nano-delivery system (QUE-KAE-NPs) for synergistic encapsulation and targeted delivery. The optimal ratio of the two active ingredients was determined to be 2:1, with a carrier ratio of 1:1, yielding nanoparticles with small particle size and high stability. Characterization confirmed successful encapsulation, demonstrating excellent stability under various conditions and sustained-release properties in the gastrointestinal tract. Animal studies revealed that QUE-KAE-NPs significantly reduced blood glucose levels in diabetic mice, improved insulin resistance and lipid metabolism disorders, enhanced antioxidant capacity, and mitigated organ damage. This research provides a novel strategy for efficient delivery of natural hypoglycemic compounds, offering promising application prospects.

Key words: diabetes, quercetin, kaempferol, nanodelivery, zein, gum arabic