Green and Efficient Extraction of Puerarin-Enriched Extracts From Pueraria lobata via Subcritical Ethanol-Water for Multi-Target Antidiabetic Effects.

Medicinal and edible plants are promising antidiabetic candidates due to their combined nutritional and pharmacological properties. However, the disconnection between bioactive substance extraction and efficacy validation hampers the development of integrated functional interventions. Here, a green and efficient subcritical ethanol-water extraction (SEWE) system was developed to obtain puerarin-enriched extracts (PEE) from Pueraria lobata. By introducing ethanol as a green polarity-modifying co-solvent, the SEWE system enabled polarity-tunable extraction under relatively mild subcritical conditions, thereby balancing extraction efficiency and compound stability. Compared with conventional extraction methods, SEWE significantly enhanced puerarin enrichment and overall extract quality, and the resulting extracts (SEWE-P) further exhibited enhanced bioactivities, including antioxidant, enzyme inhibitory, and anti-inflammatory effects, together with intracellular ROS-scavenging capacity, while maintaining good biocompatibility in vitro. In streptozotocin-induced diabetic mice, oral administration of SEWE-P significantly improved glycemic control, enhanced insulin sensitivity, and promoted pancreatic β-cell recovery. Mechanistically, SEWE-P activated the PI3K/AKT signaling pathway to improve glucose metabolism and suppressed NF-κB-mediated inflammation and oxidative stress. Overall, this study establishes an integrated green extraction-function evaluation strategy, providing a scalable approach for the development of multifunctional plant-based antidiabetic interventions.