Chemical Constituents And Hypoglycemic Activity Of Flower From Edgeworthia Gardneri

The flower of Edgeworthia gardneri which belongs to genus edgeworthia in Thymelaeaceae family is peculiar in Tibet, the local residents usually drink tea of flower from Edgeworthia. for treatment of diabetes, high cholesterol and other chronic diseases. The flower of Edgeworthia gardneri has a good effect in reducing blood glucose levels, but the composition of flower of Edgeworthia gardneri is complex with chemical constituents few reported. The chemical constituents of Edgeworthia gardneri has not been systematically studied. The hypoglycemic activity of Edgeworthia gardneri. is only limited to crude extracts but not monomeric compounds. So its active ingredients and mechanism are not clear. Therefore, the development and application of flower from Edgeworthia gardneri in hypoglycemic drugs has been limited.A total of twenty compounds including two new ones were isolated through various separation techniques and structurally identified on the basis of diverse spectroscopic methods (NMR, MS, IR, UV) and single crystal X-ray diffraction analysis. They were four coumarins (1,2,10,17), seven flavonoids (7,8,12-16), five Phenylpropanoids (5,9,18-20), one lignan compound (11) and three benzene derivatives (3,4,6), additionally. To determine the content of compound 12, which is the most abundant and active compound in the Edgeworthia gardneri, HPLC method was used. The contents of compound 12 in the flower of Edgeworthia gardneri was 13.16%.All isolates were evaluated for their inhibitory activity against a-glucosidase in vitro. The flower extract exhibited a significant inhibitory activity with an IC50 value of 267μg/mL. Among these compounds, compound 8 was the most active, with an IC50 value of 5.1μg/mL. Compound 7 showed a potent inhibitory activity with an IC50 value of 56.2μg/mL. Compound 12 showed a moderate activity, with an IC50 value of 202μg/mL. To clarify the a-glucosidase inhibition mode of compound 12, Lineweaver-Burk plots were generated. The results indicated that compound 12 was a competitive inhibitor. According to Michaelis-Menten kinetics, the value of inhibition constant (Kt) is 0.473 mM. Also all isolates were evaluated for their inhibitory activity against α-amylase. The flower extract exhibited a significant inhibitory activity with an IC50 value of 220 μg/mL. Among these compounds, compound 8 was the most active, with an IC50 value of 7.3 μg/mL and compound 12 was the second most active, with an IC50 value of 12.02 μg/mL. The other compounds showed moderate activities. The antioxidant activity studies have shown that flavonoids isolated from the ethyl acetate phase have significant antioxidant capacity, indicating that the antioxidant activity of the flower from Edgeworthia gardneri is related to the flavonoids.To further confirm the inhibitory activity against α-glucosidase of compound 12, the oral sucrose tolerance test (OSTT) was used to evaluate the antihyperglycemic effects of compound 12 in vivo. The results showed that compound 12 significantly reduces postprandial blood glucose in normal and diabetic mice. In contrast with glibenclamide, compound 12 displayed a hypoglycemic effect in diabetic but not in normal mice. These results indicated that compound 12 may not act directly via insulin liberation, but probably involves the protection of pancreatic β-cell survival and function.