Antidiabetic and anti-obesity acylated flavonol diglucoside from Ammannia baccifera L. subsp. aegyptiaca (Willd.) Koehne Waste

Abstract Chemical investigation of the aerial parts of Ammania aegyptiaca ethanol extract (AEEE) revealed significant high concentrations of polyphenols and flavonoids content with notable antioxidant activity in DPPH, ORAC, and reducing power assay. New acylated diglucoside flavonol myricetin 3-O-β-4­C1-(6"-O-galloyl glucopyranoside) 7-O-β-4C1-glucopyranoside (MGGG) was isolated from aerial parts of AEEE along with four additional known phenolics, not characterized previously from AEEE. Moreover, powerful inhibitory effects of MGGG, AEEE, and all isolates against α-amylase, pancreatic lipase and β-glucosidase, were assessed. In addition, flexible molecular docking was used to reveal the inhibition towards digestive enzymes and confirmed that the MGGG interacted strongly with the active site residues of these enzymes with the highest binding free energy against β-glucosidase (DG=-8.98 kcal/mol) compared to the commercial drug Acarbose, thus justifying its dual management of diabetes and obesity. In streptozotocin (STZ) induced diabetic rats, AEEE significantly decreased high serum glucose, α-amylase activity, liver and kidney function markers and increased insulin level. Moreover, it improved lipid profile due to diabetes with increased SOD activity and inhibited of TBARS formation. Consequently, AEEE and MGGG are found useful in controlling the secondary complications associated with type 2 diabetes mellitus. Histopathological studies proved the decrease in the pancreas damage and agreed with the biochemical findings. These results provide evidence that AEEE and MGGG have potent antidiabetic activity, which warrants additional investigations.