Screening and Elucidation of Chemical Structures of Novel Mammalian α-Glucosidase Inhibitors Targeting Anti-Diabetes Drug from Herbals Used by E De Ethnic Tribe in Vietnam

Among ten extracts of indigenous medicinal plants, the MeOH extract of Terminalia triptera Stapf. (TTS) showed the most efficient mammalian alpha-glucosidase inhibition for the first time. The data of screening bioactive parts used indicated that the TTS trunk bark and leaves extracts demonstrated comparable and higher effects compared to acarbose, a commercial anti-diabetic drug, with half-maximal inhibitory concentration (IC50) values of 181, 331, and 309 mu g/mL, respectively. Further bioassay-guided purification led to the isolation of three active compounds from the TTS trunk bark extract and identified as (-)-epicatechin (1), eschweilenol C (2), and gallic acid (3). Of these, compounds 1 and 2 were determined as novel and potent mammalian alpha-glucosidase inhibitors. The virtual study indicated that these compounds bind to alpha-glucosidase (Q6P7A9) with acceptable RMSD values (1.16-1.56 angstrom) and good binding energy (DS values in the range of -11.4 to -12.8 kcal/mol) by interacting with various prominent amino acids to generate five and six linkages, respectively. The data of Lipinski's rule of five and absorption, distribution, metabolism, excretion and toxicity (ADMET)-based pharmacokinetics and pharmacology revealed that these purified compounds possess anti-diabetic drug properties, and the compounds are almost not toxic for human use. Thus, the findings of this work suggested that (-)-epicatechin and eschweilenol C are novel potential mammalian ff-glucosidase inhibitor candidates for type 2 diabetes treatment.

Automated summary

Among indigenous medicinal plants, the MeOH extract of Terminalia triptera Stapf. (TTS) showed the most efficient mammalian alpha-glucosidase inhibition for the first time. Three active compounds, including (-)-epicatechin, eschweilenol C, and gallic acid, were isolated from TTS and determined as novel and potent mammalian alpha-glucosidase inhibitors. In silico studies revealed that these compounds bind to alpha-glucosidase with good binding energy and interact with prominent amino acids. The purified compounds possess anti-diabetic drug properties and low toxicity, making them potential candidates for type 2 diabetes treatment.