Zhu Xiaoxia, Jing Linlin, Chen Chun, Shao Meng, Fan Qin, Diao Jianxin, Liu Yuanliang, Lv Zhiping, Sun Xuegang
Department of Traditional Chinese Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China; The Key Laboratory of Molecular Biology, State Administration of Traditional Chinese Medicine, School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, China.
Traditional Chinese Medicine Integrated Hospital, Southern Medical University, Guangdong, Guangzhou 510305, China.
J Ethnopharmacol. 2015 Feb 3;160:86-93. doi: 10.1016/j.jep.2014.11.031. Epub 2014 Nov 27.
Danzhi Xiaoyao San (DXS) is a canonical Chinese medicine formula from Principles 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).
Chemical 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.
DXS 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.
DXS 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.
丹栀逍遥散（DXS）是明代所著《内科摘要》中的经典中药方剂。该方剂已获批准并商业化用于预防和治疗情感障碍。本研究旨在探讨以下假说：丹栀逍遥散通过下调海马吲哚胺2,3-双加氧酶（IDO），使犬尿氨酸（Kyn）/血清素（5-HT）途径的平衡向5-HT途径转移，从而治疗抑郁样行为。
以标准提取物中栀子苷、芍药苷、阿魏酸、丹皮酚和藁本内酯的化学指纹图谱作为丹栀逍遥散的物质基础。将慢性不可预测轻度应激（CUMS）诱导的抑郁样行为大鼠随机分为四组，即对照组、模型组、丹栀逍遥散组和氟西汀组。分别采用酶联免疫吸附测定、蛋白质免疫印迹法和液相色谱-电喷雾电离串联质谱法分析细胞因子、IDO和色氨酸（Trp）代谢产物。
丹栀逍遥散显著增加了穿越格子数、蔗糖消耗量和体重。该治疗显著降低了血清肿瘤坏死因子-α和白细胞介素6（IL-6）水平。然而，丹栀逍遥散对IL-1β、IL-2和干扰素γ无显著影响。丹栀逍遥散下调了海马中IDO的活性及随后Kyn的生成。该治疗上调了海马中Trp和5-HT的含量，但不影响5-HT的周转率。
丹栀逍遥散对暴露于CUMS的大鼠表现出抗抑郁样作用。丹栀逍遥散降低IDO活性，使Kyn/5-HT途径的平衡向5-HT途径转移。
