Danzhi Xiaoyao San ameliorates depressive-like behavior by shifting toward serotonin via the downregulation of hippocampal indoleamine 2,3-dioxygenase
Danzhi Xiaoyao San ameliorates depressive-like behavior by shifting toward serotonin via the downregulation of hippocampal indoleamine 2,3-dioxygenase
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丹栀逍遥散通过下调海马吲哚胺 2,3-双加氧酶而转向血清素，从而改善抑郁样行为
DOI：
10.1016/j.jep.2014.11.031
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发表时间：
2015
影响因子：
5.4
通讯作者：
Sun Xuegang
中科院分区：
文献类型：
--
作者：
Zhu Xiaoxia;Jing Linlin;Chen Chun;Shao Meng;Fan Qin;Diao Jianxin;Liu Yuanliang;Lv Zhiping;Sun Xuegang
民族药理学相关性 丹栀逍遥散（DXS）是明代成书于《内科原理》的经典中药方剂。该配方已被批准并商业化用于预防和治疗情感障碍。本研究旨在探讨 DXS 通过下调海马吲哚胺 2,3-双加氧酶 (IDO) 将犬尿氨酸 (Kyn)/血清素 (5-HT) 途径的平衡转向 5-HT 途径来治疗抑郁样行为的假设。 材料和方法 栀子苷、芍药苷、阿魏酸、丹皮酚和以标准提取物藁本内酯作为DXS的原料基础。将慢性不可预测性轻度应激（CUMS）诱导的抑郁样行为大鼠随机分为四组，即对照组、模型组、DXS组和氟西汀组。分别通过酶联免疫吸附测定、蛋白质印迹和液相色谱-电喷雾电离串联质谱分析细胞因子、IDO 和色氨酸 (Trp) 分解代谢物。结果DXS 显着增加了穿过网格的数量、蔗糖消耗和体重。这种治疗显着降低了肿瘤坏死因子-α 和白细胞介素 6 (IL-6) 的血清水平。然而，DXS 对 IL-1β、IL-2 和干扰素 γ 没有显着影响。 DXS 下调了海马中 IDO 的活性以及随后 Kyn 的产生。这种治疗上调了海马色氨酸和 5-HT 的含量，但不影响 5-HT 周转。结论 DXS 对暴露于 CUMS 的大鼠表现出抗抑郁样作用。 DXS 降低 IDO 活性，将 Kyn/5-HT 途径的平衡转向 5-HT 途径。
Ethnopharmacological relevanceDanzhi Xiaoyao San (DXS) is a canonical Chinese medicine formula fromPrinciples of Internal Medicine, which was written during the Ming dynasty. This formula is approved and commercialized for use in the prevention and treatment of affective disorders. This study is aimed to investigate the hypothesis that DXS treats depressive-like behavior by shifting the balance of the kynurenine (Kyn)/serotonin (5-HT) pathway toward the 5-HT pathway through the downregulation of hippocampal indoleamine 2,3-dioxygenase (IDO).Materials and methodsChemical fingerprints of gardenoside, paeoniflorin, ferulic acid, paeonol, and ligustilide in standard extraction were used as the material bases of DXS. Rats with depressive-like behavior induced by chronic unpredictable mild stress (CUMS) were randomly divided into four groups, namely the control, model, DXS, and fluoxetine groups. Cytokines, IDO, and tryptophan (Trp) catabolites were analyzed by enzyme-linked immunosorbent assay, western blot, and liquid chromatography–electrospray ionization tandem mass spectrometry, respectively.ResultsDXS significantly increased crossing grid numbers, sucrose consumption, and body weight. This treatment significantly decreased the serum levels of tumor necrosis factor-α and interleukin 6 (IL-6). However, DXS elicited no significant effects on IL-1β, IL-2, and interferon γ. DXS downregulated the activity of IDO and subsequent production of Kyn in the hippocampus. This treatment upregulated the hippocampal contents of Trp and 5-HT but did not influence 5-HT turnover.ConclusionsDXS exhibited antidepressant-like effects on rats exposed to CUMS. DXS reduced IDO activity to shift the balance of the Kyn/5-HT pathway toward the 5-HT pathway.