Laleh KHODAIE, Maryam HELALI, Mostafa ZAKARIAZADEH, Hossein NAZEMIYEH, Hadi GHANBARI, Faride RANJBARI, Somaieh SOLTANI
Journal of Research in Pharmacy - 2026;30(4):1087-1103
Traditional Persian Medicine (TPM) manuscripts have introduced Heracleum persicum (Golpar) fruits to alleviate dementia. This study aimed to investigate the AChE inhibitory activity of essential oil and methanolic extract of fruits of Golpar and isolate their active phytochemicals and perform in silico study on the plant's isolated compounds. AChE inhibitory activity was performed by Ellman's test. The major phytochemicals of volatile oil and extract were isolated and identified using GC-MS, UV-Vis, 1H NMR, and 13C NMR. Molecular docking studies of the isolated compounds were performed using AutoDock software. The AChE inhibitory activity of the methanolic extract and essential oil was 63.86%+/-2.57 and 54.67%+/-1.04, respectively. Octyl acetate (8.51%) and hexyl butyrate (11.51%) (aliphatic esters) were dominant compounds of volatile oil, while bergapten and methoxsalen (psoralen derivatives) were identified from the methanolic extract. Psoralen derivatives showed a high affinity to AChE than aliphatic esters. The lowest free binding energy of bergapten, methoxsalen, octyl acetate, and hexyl butyrate with AChE were -5.46, -5.12, -4.29, and -4.19 kcal/mol, respectively. More hydrophobicity of aliphatic esters may contribute to decrease in interaction potency with the enzyme in comparison to psoralen derivatives. A methoxy functional group in C5 and C8 positions of bergapten and methoxsalen can affect the binding capacity to AChE. the results of docking comply with the results of the experimental study. Psoralen derivatives showed high affinity than aliphatic esters. Especially bergapten, showed higher affinity to AChE. It is rational to see higher inhibitory activity in the methanolic extract than volatile oil.
