Extraction And Hypoglycemic Activity Of Flavonoids In Ficus Carica Leaves

Aims: To study the extraction process of total flavones from Ficus Carica leaves, determining essential ingredients; optimize the diabetes mellitus model in C57BL/6J mice induced by streptozotocin(STZ); compare the hypoglycemic effect of four different strains of extractions from Ficus Carica leaves and explore the hypoglycemic effect of different doses of extraction from Ficus Carica leaves and the specific mechanism.Methods: 1. Total flavones from Ficus Carica leaves was extracted by ethanol extraction method with ultrasound-assisted and the extraction technology was optimized by orthogonal design. Effective methods for content determination was compared and identified. Main ingredients of extractions was determined by gas chromatography-mass spectrometry and ultra performance liquid chromatography assay. 2. Different diabetes models of C57BL/6J mice were established with different doses of STZ intraperitoneal administration combined with or without 4-week high fat diet. Weight, Water-drinking, food-consuption and blood glucose was follow-up for stability analysis. 3. With C57BL/6J diabetic mice(STZ celiac injection, 150 mg/kg for a single time), randomly grouping, blood glucose, serum lipid were detected and pathological changes of pancreas and kidney was observed, after intragastric administration of four different strains of extraction. 4. C57BL/6J diabetic model(STZ celiac injection, 180 mg/kg for a single time), randomly grouping, were given metformin or different doses of extraction from Ficus Carica leaves. Negative and positive controls were given distilled water of equal volume. Followed-up for 6 weeks, blood glucose, lipid, insulin, hepatic glycogen and activity of Glucose-6-phosphatase and glycogen phosphorylase of mice in different groups were determined and pathological changes of pancreas was observed.Results: 1. The optimal process ethanol extraction with ultrasound-assisted for total flavonoids extraction from Ficus carica leaves was as follows: defatted by a 5-fold amount of petroleum ether with ultrasonic oscillation for 10 min(3 repeats), incubated in 50 L ethanol(40 %) and subjected to ultrasonic extraction( power 400 W, 30 min, temperature 70 °C). The average extracted efficiency was 27.86 %. Al(NO3)3-Na NO2-Na OH colorimetric method was effective for contents analyzing and the average content was 9.49 %. The main components of extractions were rutin, psoralen, and bergamot glycoside lactone. 2. STZ 180 mg/kg single dose and four weeks high-fat diet combined with STZ 150 mg/kg single dose administration or 200 mg/kg two times administration induced diabetic models were more stable in the long run. 3. Blood glucose in four groups intervened with different strains of Ficus carica leaves decreasd and triglyceride levels in Feng Chan Huang, Zi Guo, and the Japanese Zi Guo groups reduced. Moreover, pathological features of the pancreas in Feng Chan Huang and Mei Li Ya groups was somewhat ameliorated. 4. Blood glucose of diabetic mice in each dose group reduced with cholesterol unchanged. Triglycerides were significantly reduced in high dose group. Pancreatic pathology was improved to some extent in each dose group with a dose-dependent manner. Liver glycogen content and glucose-6-phosphatase activity decreased significantly in medium and high dose group with no significant difference in insulin levels.Conclusions: Ethanol extraction with ultrasound-assisted is effective for total flavones extraction from Ficus Carica leaves. In STZ-induced diabetic mice, extraction from Ficus Carica leaves showed significant hypoglycemic and slightly hypolipidemic effect, as well as amelioration of pancreas pathological damages. Feng Chan Huang was optimal among the four strains. Glucose-6-phosphatase activity and liver glycogen level was the possible adjustments in the hypoglycemic effect of total flavones extracted from Ficus Carica leaves.