Prediction on the mechanism of agarwood sesquiterpene components in prevention and treatment of insomnia based on molecular docking

WANG Can-hong; GONG Bao; WU Yu-lan; MOU Jun-yu; CHENG Xiao-ling; WEI Jian-he

doi:10.20251/j.cnki.1003-3734.2025.19.008

Abstract：Objective:Agarwood has been widely used in incense since ancient times.It has the effect of sedation and tranquilization.Modern pharmacological studies have shown that agarwood has a good sleep-promoting effect,and its active components are mainly sesquiterpene compounds.But the mechanism of action has not been explained.In this study,molecular docking technology was used to verify the mechanism of action and the possible drug targets of agarwood sesquiterpene compounds for insomnia prevention and treatment.Methods:Agarwood sesquiterpenoids,key targets of insomnia prevention and treatment,as well as their structural formulas,were obtained through the database,and the chemical components and their targets were verified by molecular docking using AutoDock software.Results:A total of 186 agarwood sesquiterpene compounds were collected and scored by interlinking with key targets through molecular docking.The threshold value of affinity≤-5 kcal·mol-1 was generally selected.The lower the score is,the higher affinity between ligand and receptor was obtained,which was considered as potential affinity.The conformation with the lowest affinity was used as the best docking conformation and visualized.Molecular docking found that five of the 186 compounds were highly bound to eight selected key targets.The neuroprotective activity of five compounds(G32,G39,G40,G41,M18)was screened in vitro with the IC50 of(6.22±0.35),(5.72±0.22),(4.37±0.56),(4.03±0.26),and(3.05±0.13)μmol·L-1,respectively.The IC50 value of the positive drug diazepam was 3.12 μmol·L-1,and the neuroprotective effect of compound M18 was slightly greater than that of positive drug.Conclusion:The study showed that some reported agarwood sesquiterpene compounds could be highly combined with insomnia related targets,which provides scientific data and reference for the study of molecular mechanism and pharmacoactive substances of agarwood for the prevention and treatment of insomnia.