Xanthones as α-glucosidase inhibitors from the antihyperglycemic extract of Securidaca inappendiculata

Abstract

Context: Securidaca inappendiculata Hassk. (SI) is used to cure fractures and rheumatoid arthritis in China. Also, it is a potential antidiabetes drug; however, there are no reports on this.

Objective: The study was designed to evaluate the antihyperglycemic activities of fractions and compounds from SI, and attempt to explore the mechanism.

Materials and methods: Antihyperglycemic activities were evaluated by the suppression on serum glucose levels in vivo and α-glucosidase inhibition assays in vitro. Fractions were given to mice by gastric intubation for 8 d. The high, medium, and low doses of fractions were equal to 10, 5, and 2.5 g/kg of the herb [SID (dichloromethane fraction) and SIE (ethyl acetate fraction) were doubled]. The serum glucose was monitored at 1 and 12 h after feeding. The silica gel and LH-20 chromatography were used to isolate active compounds. Structure–activity relationship analysis was based on IC₅₀s and structures.

Results: The IC₅₀s of SID, SIE, SIA (acetone fraction), SIM (methanol fraction), and acarbose were 712, 446, 1123, 1418, and 735 μg/mL. The postprandial and fasting serum glucose levels of SID, SIE, SIA, and SIM (high dose) were 5.5, 5.9, 6.2, 6.3 and 3.7, 3.5, 4.0, 5.0 mmol/L, while those of vehicle control were 7.5 and 5.6 mmol/L. Eleven xanthones isolated all exhibited inhibitory activities, mainly in a non-competitive reversible manner. The IC₅₀s varied from 3.2 to 77.3 μg/mL. Structure–activity relationship analysis exhibited free hydroxyls contributed the most importance to the activity.

Conclusion: The results indicated that xanthones from SI were powerful agents for antidiabetes.

• Activity screening
• antidiabetes
• material base
• structure–activity relationship analysis