Antidiabetic Activity and In Silico Molecular Docking of Polyphenols from Ammannia baccifera L. subsp. Aegyptiaca (Willd.) Koehne Waste: Structure Elucidation of Undescribed Acylated Flavonol Diglucoside

Abstract

Chemical investigation of the aerial parts of Ammania aegyptiaca ethanol extract (AEEE) showed high concentrations of polyphenol and flavonoid content, with notable antioxidant activity. Undescribed acylated diglucoside flavonol myricetin 3-O-β-⁴C₁-(6″-O-galloyl glucopyranoside) 7-O-β-⁴C₁-glucopyranoside (MGGG) was isolated from the aerial parts of AEEE, along with four known polyphenols that had not been characterized previously from AEEE. The inhibitory effects of MGGG, AEEE, and all compounds against α-amylase, pancreatic lipase and β-glucosidase were assessed. In addition, molecular docking was used to determine the inhibition of digestive enzymes, and this confirmed that the MGGG interacted strongly with the active site residues of these enzymes, with the highest binding free energy against α-amylase (-8.99 kcal/mol), as compared to the commercial drug acarbose (-5.04 kcal/mol), thus justifying its use in the potential management of diabetes. In streptozotocin (STZ)-induced diabetic rats, AEEE significantly decreased high serum glucose, α-amylase activity and serum liver and kidney function markers, as well as increasing insulin blood level. Moreover, AEEE improved the lipid profile of diabetic animals, increased superoxide dismutase (SOD) activity, and inhibited lipid peroxidation. Histopathological studies proved the decrease in pancreas damage and supported the biochemical findings. These results provide evidence that AEEE and MGGG possess potent antidiabetic activity, which warrants additional investigation.

Keywords: Ammania aegyptiaca; diabetes; digestive enzymes; molecular docking; myricetin 3-O-β-4C1-(6″-O-galloylglucopyranoside) 7-O-β-4C1-glucopyranoside.

Figure 1

Myricetin3-O-β-⁴C₁-(6′′-O-galloylglucopyranoside)-7-O-β-⁴C_1-glucopyranoside (1), kaempfeol 3-O-rutinoside (2), quercetin 3-O-rutinoside (3), tellimagranidine-I (4) and 2,3-α, β-digalloy glucose (5).

Figure 2

Molecular docking interactions of isolated compounds (1–5) with amino acid residues in the active site of α-amylase as 3D diagram. (a) Standard Acarbose (b) MGGG (c) Kaempfeol 3-O-rutinoside (d) Quercetin 3-O-rutinoside (e) Tellimagranidine-I (f) 2,3-α, β-digalloy glucose. The green dashed lines stand for hydrogen bonds and the purple dashed lines stand for pi interactions.

Figure 3

Molecular docking interactions of isolated compounds (1–5) with amino acid residues in the active site of β-glucosidase as 3D diagram. (a) Standard Acarbose (b) MGGG (c) Kaempfeol 3-O-rutinoside (d) Quercetin 3-O-rutinoside (e) Tellimagranidine-I (f) 2,3-α, β-digalloy glucose. The green dashed lines stand for hydrogen bonds and the purple dashed lines stand for pi interactions.

Figure 4

Molecular docking interactions of isolated compounds (1–5) with amino acid residues in the active site of pancreatic lipase as 3D diagram. (a) Standard Acarbose (b) MGGG (c) Kaempfeol 3-O-rutinoside (d) Quercetin 3-O-rutinoside (e) Tellimagranidine-I (f) 2,3-α, β-digalloy glucose. The green dashed lines stand for hydrogen bonds and the purple dashed lines stand for pi interactions.

Figure 5

Mapping surface showing MGGG occupying the active pocket of α-amylase (a), β-glucosidase (b) and pancreatic lipase (c), respectively.

Figure 6

Reducing power of AEEE and isolated compounds (1–5) compared with quercetin as standard. Results are given as mean ± SD of three replicate analyses.

Figure 7

(A) Effect of AEEE on body weight during the experimental period (28 days). (B) Effect of AEEE on serum liver and kidney function markers. Results are stated as mean ± S.D. (n = 6). Results are considered significantly different at p < 0.05. (a) is statistically different from NC group; (b) is statistically different from DC group.

Figure 8

(A) Effect of AEEE on serum blood glucose, insulin and α-amylase. (B)Effect of AEEE on serum lipid profile. (C) Effect of AEEE on oxidative stress markers of pancreas. Results are stated as mean ± S.D, (n = 6). Results are considered significantly different at p < 0.05. (a) is statistically different from NC group; (b) is statistically different from DC group.

Figure 9

The histological investigation of pancreas. (A–C): Pancreas sections of NC, AE500-NC and AE 250-NC groups respectively, showing dense staining acinar cells and a light-staining islet of Langerhans; (D): Diabetic rat showing the acinar cells around the islets though seemed to be in normal proportion with up normal morphology with shrunken islet is and intra islet hemorrhage (blue arrow). (E): Diabetic rat showing degenerative islet of Langerhans (asterisk) with different vacuoles size (long arrow) and hemorrhage (short arrow); (F,G): AE 500-DC rat showing the exocrine pancreas appearing.