In Vitro and Molecular Docking Evaluation of the Anticholinesterase and Antidiabetic Effects of Compounds from Terminalia macroptera Guill. & Perr. (Combretaceae)

Alzheimer's disease (AD) and diabetes are non-communicable diseases with global impacts. Inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) are suitable therapies for AD, while α-amylase and α-glucosidase inhibitors are employed as antidiabetic agents. Compounds were isolated from the medicinal plant and evaluated for their AChE, BChE, α-amylase, and α-glucosidase inhibitions. From H and C NMR data, the compounds were identified as 3,3'-di-O-methyl ellagic acid ( ), 3,3',4'-tri-O-methyl ellagic acid-4-O-β-D-xylopyranoside ( ), 3,3',4'-tri-O-methyl ellagic acid-4-O-β-D-glucopyranoside ( ), 3,3'-di-O-methyl ellagic acid-4-O-β-D-glucopyranoside ( ), myricetin-3-O-rhamnoside ( ), shikimic acid ( ), arjungenin ( ), terminolic acid ( ), 24-deoxysericoside ( ), arjunglucoside I ( ), and chebuloside II ( ). The derivatives of ellagic acid ( - ) showed moderate to good inhibition of cholinesterases, with the most potent being 3,3'-di-O-methyl ellagic acid, with IC values of 46.77 ± 0.90 µg/mL and 50.48 ± 1.10 µg/mL against AChE and BChE, respectively. The compounds exhibited potential inhibition of α-amylase and α-glucosidase, especially the phenolic compounds ( - ). Myricetin-3-O-rhamnoside had the highest α-amylase inhibition with an IC value of 65.17 ± 0.43 µg/mL compared to acarbose with an IC value of 32.25 ± 0.36 µg/mL. Two compounds, 3,3'-di-O-methyl ellagic acid (IC = 74.18 ± 0.29 µg/mL) and myricetin-3-O-rhamnoside (IC = 69.02 ± 0.65 µg/mL), were more active than the standard acarbose (IC = 87.70 ± 0.68 µg/mL) in the α-glucosidase assay. For α-glucosidase and α-amylase, the molecular docking results for reveal that these compounds may fit well into the binding sites of the target enzymes, establishing stable complexes with negative binding energies in the range of -4.03 to -10.20 kcalmol . Though not all the compounds showed binding affinities with cholinesterases, some had negative binding energies, indicating that the inhibition was thermodynamically favorable.