RESUMEN
Triterpene acids, the main component of Corni Fructus, could improve diabetes mellitus, for which the underlying hypoglycemic mechanism is still unclear, in patients. In this study, total triterpenoid acids were extracted by ultrasonic-microwave assisted extraction optimized by the response surface methodology. The extract was then purified with an X-5 macroporous resin, and the yield of total triterpenoid acids increased to 281.24 mg g-1 as compared with the 35.71 mg g-1 obtained by unassisted extraction. The contents of five components were determined by ultrafast performance liquid chromatography. In addition, the hypoglycemic and hypolipidemic activities of total triterpenoid acids in diabetic mice induced by streptozotocin and a high fat diet were studied. The results indicated that all parameters (oral glucose tolerance, insulin resistance and liver damage) related to diabetes were significantly improved by total triterpenoid acids. Furthermore, total triterpenoid acids significantly recovered the expression level of AMP-activated protein kinase and its downstream proteins, including acetyl-CoA carboxylase, carnitine palmityltransferase-1, peroxisome proliferator-activated receptor alpha, sterol regulatory element-binding protein 1c and fatty acid synthase. Altogether, total triterpenoid acids could ameliorate hyperlipidemia and hyperglycemia in diabetic mice, probably by activating the AMP-activated protein kinase-peroxisome proliferator-activated receptor signaling pathway and inhibiting the sterol regulatory element-binding protein 1c and fatty acid synthase signaling pathways. Therefore, total triterpene acids, isolated from Corni Fructus which is a prevailing health food, could be a functional food ingredient with therapeutic and commercial values.
Asunto(s)
Cornus/química , Hipoglucemiantes/farmacología , Hipolipemiantes/farmacología , Microondas , Extractos Vegetales/farmacología , Triterpenos/metabolismo , Ultrasonido/métodos , Proteínas Quinasas Activadas por AMP/metabolismo , Animales , Diabetes Mellitus Experimental/tratamiento farmacológico , Dieta Alta en Grasa , Prueba de Tolerancia a la Glucosa , Humanos , Hiperlipidemias/tratamiento farmacológico , Masculino , Ratones , Ratones Endogámicos ICR , PPAR alfa/metabolismo , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/metabolismoRESUMEN
Accumulating evidence suggests that gut microbiota plays a crucial role in the development of metabolic diseases, especially type 2 diabetes mellitus (T2DM). The nutrient-rich resource Cornus Fructus (CF) showed curative effects on diabetes mellitus. However, the mechanism underlying its hyperglycemic activity remains obscure. Herein, the antidiabetic potential of four extracts from CF, including saponin (CTS), iridoid glycoside (CIG), tannin (CT), and alcohol extract (CCA) was evaluated in vivo. The results showed that all four extracts could increase the body weight, decrease the blood glucose levels, and elevate the glucose tolerance. Moreover, insulin sensitivity and lipid profile were significantly improved in fed mice. In the [Formula: see text]-diversity index of samples, compared to the DM group, the diversity and richness of gut microbiota in mice to a certain extent were reduced in both CF extracts and Metformin (PC). Among them, there was statistical significance in PC (ACE, [Formula: see text]) and CCA (ACE, [Formula: see text]; chao1: [Formula: see text]). Beta diversity showed the same trend as the UPGMA clustering trees, which revealed that CF extracts could improve intestinal homeostasis in T2DM mice. Also, CF extracts could elevate the production of short-chain fatty acids, as well as regulate the composition of gut microbiota. The key bacteria related to T2DM including Firmicutes, Bacteroides, Lactobacillus, and Clostridium were modulated by metformin and CF. Altogether, CF is a potential nutrient-rich candidate that can be used in functional foods for the treatment of T2DM, and the change of gut microbiota might be a novel mechanism underlying its hyperglycemic activity.
Asunto(s)
Cornus/química , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/microbiología , Microbioma Gastrointestinal/efectos de los fármacos , Fitoterapia , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Animales , Glucemia/metabolismo , Peso Corporal/efectos de los fármacos , Diabetes Mellitus Tipo 2/etiología , Modelos Animales de Enfermedad , Alimentos Funcionales , Resistencia a la Insulina , Glicósidos Iridoides , Metabolismo de los Lípidos/efectos de los fármacos , Masculino , Ratones Endogámicos ICR , Extractos Vegetales/química , Saponinas , TaninosRESUMEN
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.