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

Abstract

Among ten extracts of indigenous medicinal plants, the MeOH extract of Terminalia triptera Stapf. (TTS) showed the most efficient mammalian α-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 µg/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 α-glucosidase inhibitors. The virtual study indicated that these compounds bind to α-glucosidase (Q6P7A9) with acceptable RMSD values (1.16–1.56 Å) 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 α-glucosidase inhibitor candidates for type 2 diabetes treatment.

Assessment of the Chemical Profile and Potential Medical Effects of a Flavonoid-Rich Extract of Eclipta prostrata L. Collected in the Central Highlands of Vietnam

“…The molecular docking study was performed following the protocol presented in previous reports [54,65]. The protein structure data of the enzyme 1EEA were obtained from the Worldwide Protein Data Bank (https://www.rcsb.org/structure/3qpc, accessed on 7 August 2023) for the preparation of the 3D structure by using MOE-2015.10 software.…”

“…Lipinski's Rule of Five has been wildly utilized for evaluating the drug-likeness of an inhibitor compound when considering its further development as a drug [54,64,65]. Lipinski's Rule of Five includes "mass < 500 Da, LogP value < 5, H-donor linkages < 5, H-acceptors linkages < 10, and the molar refractivity values in the range of 40-130".…”

“…Lipinski's Rule of Five includes "mass < 500 Da, LogP value < 5, H-donor linkages < 5, H-acceptors linkages < 10, and the molar refractivity values in the range of 40-130". A compound satisfying ≥2 of these criteria is suggested to show drug-like properties [64,65]. The data are presented in Table 8.…”