Alpha-Glucosidase Inhibition and Molecular Docking of Isolated Compounds from Traditional Thai Medicinal Plant, Neuropeltis racemosa Wall

Abstract

Neuropeltis racemosa Wall. (Convolvulaceae) is wildly distributed in Asia. Its stem is used as the component in traditional Thai recipes for treatments of muscle rigidity, skin disorder, dysentery, and hypoglycemia. However, the chemical constituents and biological activities of N. racemosa have not been reported. From a screening assay, N. racemosa stem crude extract showed the potent effect on alpha-glucosidase inhibition at 2 mg/mL as 96.09%. The bioassay-guiding isolation led to 5 compounds that were identified by spectroscopic techniques as scopoletin (1), syringic acid (2), methyl 3-methyl-2-butenoate (3), N-trans-feruloyltyramine (4), and N-trans- coumaroyltyramine (5). Compounds 1, 4, and 5 exhibited an IC₅₀ of 110.97, 29.87, and 0.92 µg/mL, respectively, while the IC₅₀ of positive standard, acarbose was 272.72 µg/mL. Kinetic study showed that compound 1 performed as the mixed-type inhibition mechanism, whereas compounds 4 and 5 displayed the uncompetitive inhibition mechanism. The docking study provided the molecular understanding of isolated aromatic compounds (1, 2, 4 and 5) to alpha-glucosidase. Hence, this study would be the first report of isolated compounds and their anti-alpha-glucosidase activity with the mechanism of action from N. racemosa. Thus, these active compounds will be further studied to be the lead compounds among natural antidiabetic drugs.

Keywords: Neuropeltis racemosa; alpha-glucosidase inhibition; anti-diabetes; molecular docking; phytochemistry.

Figure 1

Isolated compounds (1–5) from N. racemosa stem.

Figure 2

HMBC correlations (from H to C) of compound 1.

Figure 3

HMBC correlations (from H to C) of compound 3.

Figure 4

Lineweaver−Burk plots of compound 1, 4, 5, and acarbose, respectively (A–D). The secondary plots of each compound are on the right.

Figure 5

The molecular interaction between the alpha-glucosidase, presented in grey color and glucose as in red color, 1 as in yellow color, 2 as in pink color, 4 in blue color and 5 as in orange color, respectively. (A) The molecular interaction between the alpha-glucosidase and the mentioned. (B) The expanded picture at the active site of the alpha-glucosidase. The dashed circle in yellow color indicated the entrance gate to the active site, while the red arrow was used to emphasis this gate. (C) The comparison between the docked conformations of 4 in blue color and 5 as in orange color at the entrance gate of the active site. (D,E) The alteration of the docked conformation between 4 as in blue color and 5 as in orange color. The red dashed lines indicated the X and Y-axis, while the black arrows indicated the changing of the position in the chemical structure.