Identification and Neuroprotective Evaluation of Phytoconstituents from Ailanthus excelsa: In Silico Docking and In Vitro Acetylcholinesterase Inhibition Assay

Abstract The plant Ailanthus excelsa exhibits considerable antioxidant, cytotoxic, and anti-inflammatory effects. The present study aimed to characterize the bioactive phytoconstituents of A. excelsa and evaluate their neuroprotective potential through in silico modeling and in vitro acetylcholinesterase (AChE) inhibition assay. Based on the peaks obtained from Fourier-transform infrared spectroscopy (FTIR) analysis, thirteen distinct functional groups corresponding to potential phytoconstituents were identified in A. excelsa . The identified phytoconstituents obeyed Lipinski’s Rule of Five and were further evaluated via in silico docking studies against the acetylcholinesterase target enzyme using AutoDock 4.2 software. Rivastigmine, a standard cholinesterase inhibitor, was used to compare the enzyme inhibitory potentials of the selected compounds. The computational in silico investigation revealed that the compounds possessed excellent docking scores and favorable binding orientations with the acetylcholinesterase enzyme, outperforming the standard drug. A uniform decrease in binding energy was observed for all phytoconstituents against the target enzyme, with values ranging from − 8.36 kcal/mol to -3.82 kcal/mol. Specifically, docking results demonstrated that 4-hydroxycoumarin and ferulic acid possessed notable anti-cholinesterase activity compared to the other phytoconstituents and rivastigmine. In the in vitro enzyme inhibition assay, the half-maximal inhibitory concentration IC 50 of ferulic acid was found to be 7.5468 ± 1.42 µg/ml, while 4-hydroxycoumarin exhibited an IC 50 of 3.4562 ± 0.84 µg/ml, compared to 3.913 ± 0.48 µg/ml for the standard rivastigmine. In conclusion, 4-hydroxycoumarin and ferulic acid possess a potential role in neuroprotection and could be developed as promising drug candidates against neurodegenerative diseases.