Abstract：
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.
摘要：
目的通过网络药理学方法探讨白曲内酯I(ATR)的抗抑郁作用及作用靶点。对通过网络药理学分析的ATR和抑郁的相关目标进行评分(识别5-HT2A目标)。通过高架加迷宫，开放领域，尾部悬挂,强迫游泳测试,研究了患有抑郁症（慢性不可预测的轻度应激[CUMS]）的小鼠的行为变化，以及包括血清素在内的神经递质的水平，多巴胺,和去甲肾上腺素（5-HT，DA,和NE)被确定。通过小分子蛋白对接验证ATR与5-HT2A的结合。ATR改善了CUMS小鼠的行为，提高了他们的神经递质5-HT的水平，DA,NE,并对它们的神经细胞损伤起到保护作用。在5-HT2A基因敲除后,ATR未能进一步改善CUMS行为。根据小分子蛋白对接和网络药理学分析的结果,ATR通过与5-HT2A结合而充当抑制剂。ATR可以通过靶向5-HT2A改善CUMS小鼠的行为并调节神经递质。
