Lei Chaofang, Chen Zhigang, Fan Lili, Xue Zhe, Chen Jianbei, Wang Xihong, Huang Zhen, Men Yinian, Yu Mingzhi, Liu Yueyun, Chen Jiaxu
School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China.
Dongfang Hospital Affiliated to Beijing University of Chinese Medicine, Beijing, China.
Front Pharmacol. 2022 Jun 13;13:904190. doi: 10.3389/fphar.2022.904190. eCollection 2022.
Paeoniflorin (PF) represents the major bioactive constituent of the traditional Chinese medicine plant (Ranunculaceae), which has a long history as a folk medicine in Asian. Paeoniflorin, a bitter pinene monoterpene glycoside, has antidepressant effects, but its potential therapeutic mechanism has not been thoroughly explored. Experimental depression in rats was established by the chronic unpredictable mild stress (CUMS) combined with orphan method, and the efficacy of paeoniflorin on depression was evaluated by the sucrose preference test and open field test. The antidepressant mechanism of paeoniflorin was investigated by metabolomic and network pharmacology. The relevant pathways of biomarkers highlighted in metabolomics were explored, and the possible targets of paeoniflorin in the treatment of depression were further revealed through network analysis. The binding activity of paeoniflorin to key targets was verified by molecular docking. Metabolomics showed that rats with CUMS-induced depression had urine metabolic disorders, which were reversed by paeoniflorin through the regulation of metabolic pathways. Metabolites that play a key role in the function of paeoniflorin include citric acid, thiamine monophosphate, gluconolactone, 5-hydroxyindoleacetic acid and stachyose. Key predicted targets are , , and . An important metabolic pathway is the Citrate cycle (TCA cycle). Network integrative analysis in this study showed that paeoniflorin could improve depressive-like symptoms in model rats with CUMS-induced depression and overall correct the disordered metabolic profile through multiple metabolic pathways.
芍药苷（PF）是毛茛科传统中药植物的主要生物活性成分，在亚洲作为民间药物已有悠久历史。芍药苷是一种苦味的蒎烯单萜糖苷，具有抗抑郁作用，但其潜在治疗机制尚未得到充分探索。采用慢性不可预测温和应激（CUMS）联合孤养法建立大鼠实验性抑郁模型，通过蔗糖偏好试验和旷场试验评估芍药苷的抗抑郁效果。运用代谢组学和网络药理学研究芍药苷的抗抑郁机制。探索代谢组学中突出的生物标志物相关途径，并通过网络分析进一步揭示芍药苷治疗抑郁症的可能靶点。通过分子对接验证芍药苷与关键靶点的结合活性。代谢组学显示，CUMS诱导的抑郁大鼠存在尿液代谢紊乱，芍药苷通过调节代谢途径使其得到逆转。在芍药苷功能中起关键作用的代谢物包括柠檬酸、磷酸硫胺素、葡萄糖酸内酯、5-羟吲哚乙酸和水苏糖。关键预测靶点为 、 、 和 。一条重要的代谢途径是柠檬酸循环（TCA循环）。本研究的网络综合分析表明，芍药苷可改善CUMS诱导的抑郁模型大鼠的抑郁样症状，并通过多种代谢途径整体纠正紊乱的代谢谱。
