Exploring the interaction between Salvia miltiorrhiza and α-glucosidase: insights from computational analysis and experimental studies

Abstract

α-Glucosidase has emerged as an important target for type 2 diabetes mellitus. Salvia miltiorrhiza is a widely used traditional Chinese medicine. The interaction between the chemicals of S. miltiorrhiza and α-glucosidase are still not clear, and need to be deeply investigated. Herein, an integrated approach consisting of computational analysis and experimental studies was employed to illustrate the interactions between S. miltiorrhiza and α-glucosidase. Molecular docking simulations were performed to reveal the proposed binding characteristics of the chemicals identified in S. miltiorrhiza on the basis of the total docking scores and key molecular determinants for binding. The affinities of 13 representative compounds from the medicinal herb to α-glucosidase were predicted and then confirmed by enzyme inhibitory assay in vitro. The obtained results suggested that two compounds including salvianolic acid C and salvianolic acid A in S. miltiorrhiza showed potent α-glucosidase inhibitory activity with IC₅₀ values of 4.31 and 19.29 μM, respectively. The active inhibitor, salvianolic acid C, exerted a mixed-competitive inhibition mode when binding to α-glucosidase. Such findings could be helpful to efficiently discover bioactive molecules from complex natural products, which suggests the usefulness of the integrated approach for this scenario.

Fig. 1. The chemical structures of the known α-glucosidase inhibitors.

Fig. 2. Molecular docking results of compounds SAC (A), SAA (B) and UA (C) binding to α-glucosidase (PDB code: 3 A4A). View of superimposed docking conformations for the molecules binding to the active pocket of α-glucosidase (D). Key residues are shown as stick models, and hydrogen bonds are labeled as red dashed lines. Compounds SAC, SAA and UA are colored as red, blue and cyan, respectively.

Fig. 3. Inhibitory effects of SAA, SAC, quercetin and acarbose on α-glucosidase. Each point indicates the average ± S.D. of triplicate measurements.

Fig. 4. Steady-state kinetic analysis of α-glucosidase by compounds SAC (A and C) and SAA (B and D). Lineweaver–Burk plots in the absence of compounds or at the different concentrations of compounds. Inset, K_i and values were obtained from secondary plots of the slopes of the Lineweaver–Burk plots and the apparent 1/V_maxversus the inhibitor concentrations, respectively. Each point indicates the average value from three independent experiments.