%0 Journal Article
%T Atractylenolide I improves behaviors in mice with depression-like phenotype by modulating neurotransmitter balance via 5-HT2A.
%A Pei H
%A Du R
%A He Z
%A Bi J
%A Zhai L
%A Shen H
%J Phytother Res
%V 38
%N 1
%D 2024 Jan 19
%M 37857401
%F 6.388
%R 10.1002/ptr.8045
%X To explore the antidepressant effects and targets of atractylenolide I (ATR) through a network pharmacological approach. Relevant targets of ATR and depression analyzed by network pharmacology were scored (identifying 5-HT2A targets). Through elevated plus maze, open field, tail suspension, and forced swimming tests, the behavioral changes of mice with depression (chronic unpredictable mild stress [CUMS]) were examined, and the levels of neurotransmitters including serotonin, dopamine, and norepinephrine (5-HT, DA, and NE) were determined. The binding of ATR to 5-HT2A was verified by small molecular-protein docking. ATR improved the behaviors of CUMS mice, elevated their levels of neurotransmitters 5-HT, DA, and NE, and exerted a protective effect on their nerve cell injury. After 5-HT2A knockout, ATR failed to further improve the CUMS behaviors. According to the results of small molecular-protein docking and network pharmacological analysis, ATR acted as an inhibitor by binding to 5-HT2A. ATR can improve the behaviors and modulate the neurotransmitters of CUMS mice by targeting 5-HT2A.