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Corni Fructus (CF) is a traditional medicine and beneficial food with multifaceted protective effects against diabetes and its complications. Since alpha-glucosidase inhibitors (GIs) are promising first-choice oral antihyperglycemic drugs for diabetes, we examined whether GIs from CF (GICF) are useful for diabetes treatment. Therefore, GICF was extracted by ultrasound-assisted enzymatic extraction (UAEE) that is optimized by a three-level, four-factor Box–Behnken design and determined by ultra-performance liquid chromatography. Compared to 36.31 mg g−1 without enzyme treatment, the GICF yield increased to 70.44 mg g−1via UAEE under optimum conditions (0.5% compound enzyme extracted in 23 min at 46 °C and pH 4.8). The activity (91.99%) of GICF was as predicted (93.28%). When GICF was used in an insulin-resistant HepG2 cell model, it significantly ameliorated the glucose metabolism in a dose-dependent manner. Our findings indicate that UAEE may be an innovative method for functional food extraction and a potential strategy for high-quality food ingredient (such as GI) production with high efficiency and productivity.

Saponins have been extensively used in the food and pharmaceutical industries because of their potent bioactive and pharmacological functions including hypolipidemic, anti-inflammatory, expectorant, antiulcer and androgenic properties. A lot of saponins-containing foods are recommended as nutritional supplements for diabetic patients. As a medicine and food homologous material, Corni Fructus (CF) contains various active ingredients and has the effect of treating diabetes. However, whether and how CF saponins attenuate diabetes is still largely unknown. Here, we isolated total saponins from CF (TSCF) using ultrasonic microwave-assisted extraction combined with response surface methodology. The extract was further purified by a nonpolar copolymer styrene type macroporous resin (HPD-300), with the yield of TSCF elevated to 13.96 mg/g compared to 10.87 mg/g obtained via unassisted extraction. When used to treat high-fat diet and streptozotocin-induced diabetic mice, TSCF significantly improved the glucose and lipid metabolisms of T2DM mice. Additionally, TSCF clearly ameliorated inflammation and oxidative stress as well as pancreas and liver damages in the diabetic mice. Mechanistically, TSCF potently regulated insulin receptor (INSR)-, glucose transporter 4 (GLUT4)-, phosphatidylinositol 3-kinase (PI3K)-, and protein kinase B (PKB/AKT)-associated signaling pathways. Thus, our data collectively demonstrated that TSCF could be a promising functional food ingredient for diabetes improvement.