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.

Type 2 diabetes mellitus (T2DM) is a common chronic metabolic disease. Accumulating evidence has demonstrated that nonalcoholic fatty liver disease (NAFLD) shares common typical features with T2DM, and they affect each other extensively. Thus, NAFLD has emerged as a novel target for T2DM prevention and care. Although Corni Fructus (CF) and its extracts have a therapeutic effect on T2DM, its effects and mechanisms on T2DM with NAFLD are far from elucidated. In this study, a mouse model of T2DM with NAFLD complication was established in ICR mice by feeding a high-fat, high-sugar (HFHS) diet and intraperitoneally injecting with a low dose of streptozotocin (STZ). Then, the effects of iridoid glycosides (IG) extracted from CF on this mouse model were investigated. We found that 4-week IG administration remarkably alleviated hyperglycemia and insulin resistance and significantly reduced inflammation, oxidative stress, and fat accumulation in the liver of T2DM with NAFLD mice. Further studies showed that IG inhibited the NF-κB but enhanced the PI3K-AKT signaling pathway. In summary, these results indicated that the IG from CF has potential therapeutic effects on T2DM with NAFLD.

Wine processing is a specialized technology which involves sautéing crude herbal medicine using Chinese rice wine. Herein, we identified the changes in chemical profiles and antidiabetic effects of Corni Fructus (CF) after wine processing in high-fat diet (HFD) streptozotocin- (STZ-) induced diabetic mice. A novel high-efficiency method for simultaneously quantifying gallic acid, 5-hydroxymethylfurfural, morroniside, loganin, sweroside, and cornuside by UPLC was developed, and validating crude and wine-processing CF was done for the first time. Mice were randomly divided into the following groups and orally given different solutions for 4 weeks: normal group (NC, 0.4% (w/v) CMC-Na), model group (DM, 0.4% (w/v) CMC-Na), crude CF group (CP, 3.87 g/kg), and wine-processing CF group (PP, 3.87 g/kg) followed by HFD and multiple subcutaneous injection of STZ (40 mg/kg) to induce the diabetes model except the NC group. Biochemical indexes (body weight, fasting blood glucose level, lipid level, insulin, and free fatty acid) and other parameters involving liver toxicity were measured with commercial kits and immunohistochemical method. Comparative studies on pharmacology showed that the crude extracts possess higher efficacy on hypoglycemia and hypolipidemia, while wine-processing products exhibit better effects on liver preservation. Our data suggested that wine processing was recommended when CF was used for protecting the liver; however, crude products should be used as antidiabetic drugs.

Hypoglycemic and hypolipidemic activities and underlying mechanisms of total triterpenoid acids from Corni Fructus.