Nutritional properties of extracellular vesicle-like particles from Sophora flavescens and Periplaneta americana with effects on streptozotocin-induced diabetic wound healing in rats.

INTRODUCTION

The medicinal plant Sophora flavescens (SF) and the insect Periplaneta americana (PA) have long been used in treating diabetic wounds. PA-derived extracellular vesicle-like particles (PA-EVLP) can accelerate diabetic wound healing. However, no evidence of the nutritional components and anti-diabetic wound effects of the combination of SF-EVLP with PA-EVLP (SF-PA-EVLPs) is available.

METHODS

We separated SF-EVLP and PA-EVLP via ultracentrifugation and characterized them via nano flow cytometry, transmission electron microscopy, and atomic force microscopy. Ultra-high-performance liquid chromatography coupled with mass spectrometry (UPLC/MS) was used to analyze the nutritional content of proteins, lipids, amino acids, phenols, and flavonoids in SF-EVLP and PA-EVLP. Moreover, we comprehensively evaluated the effects of SF-PA-EVLPs on wound healing and related complications in diabetic rats and systematically elucidated the underlying mechanisms.

RESULTS

The size of SF-EVLPs and PA-EVLPs was in the nanometer range, and they had a lipid bilayer structure. They contained abundant bioactive substances, lipids, proteins, and nucleic acids. In diabetic rat models, SF-PA-EVLPs had better wound healing effects than PA extract alone and significantly promoted diabetic wound healing. Concurrently, SF-PA-EVLPs had negligible effects on bone formation in streptozotocin-induced diabetic rats while ameliorating pancreatic injury. Moreover, several key substances within SF-PA-EVLPs exhibited significant enrichment in the EGFR signaling pathway with strong binding affinity.

CONCLUSION

At the dosage and treatment duration used in this study, combined therapy with SF-PA-EVLPs had stronger diabetic wound healing effects compared to clinically used PA extracts. Here, we also established the first cross-kingdom modulation system, providing a novel approach for developing nano-nutritional therapeutics based on medicinal plants, edible insects, and foods.