Medical College of Henan University of Science and Technology, Luoyang, 471023, PR China.
J Ethnopharmacol. 2020 Oct 5;260:112832. doi: 10.1016/j.jep.2020.112832. Epub 2020 May 6.
Danzhi Xiaoyao Powder (DZXY) is a classical prescription, that has been extensively used in traditional Chinese medicine (TMC) to treat depression for many years. However, the mechanism of DZXY is still unclear.
The aim was to investigate the mechanism of the antidepressant effect of DZXY on a rat model of chronic unpredictable mild stress (CUMS).
Forty male SD (Sprague-Dawley) rats with similar open field test (OFT) results were randomLy divided into a control group (n = 10) and an experimental group (n = 30). A depression model was established in the experimental group using the CUMS method. After the CUMS model was established successfully, the rats were randomLy divided into a depression model group and a DZXY group. The DZXY group was fed DZXY, while the depression model group and control group were given an equal amount of 0.5% sodium carboxymethyl cellulose suspension. Intragastric administration was performed once daily for 14 consecutive days. Animal weight, the sugar preference test, the open field test and the forced swimming test were used to evaluate the modeling effect and the antidepressant effect of DZXY. After the experiment, the plasma of rats was collected and the changes in plasma metabolites were analyzed by UPLC/Q-TOF-MS. The UPLC/Q-TOF-MS spectra data were evaluated by pattern recognition analysis to determine the changes in endogenous metabolites in the rat plasma samples.
The results of the behavioral investigation showed that the rat model of depression was successfully replicated and that DZXY had an antidepressant effect. Using the UPLC-MS/MS metabolomics platform, partial least squares (PLS) and orthogonal partial least squares (OPLS), metabolic profile models (R2 and Q2 ≥ 0.5) of rat plasma were successfully constructed. The model could distinguish among the control group, the depression model group and the DZXY group. Finally, 38 differential metabolites were identified in the plasma. According to KEGG (http://www.kegg.jp) pathway analysis, amino acid metabolism, lipid metabolism, purine metabolism, the prolactin signaling pathway and bile secretion were enriched and represented the main metabolic pathways influenced in the plasma.
This study successfully established a CUMS depression model. A total of 38 differential metabolites associated with depression were identified in the plasma of rats, 24 of which were modulated by DZXY. These results suggest that DZXY can improve excitability and play an antidepressant role by regulating phenylalanine metabolism, arachidonic acid metabolism, porphyrin metabolism, D-arginine and D-ornithine metabolism, steroid hormone biosynthesis, unsaturated fatty acid biosynthesis and steroid biosynthesis.
丹栀逍遥散（DZXY）是一种经典方剂，在中医中已广泛用于治疗抑郁症多年。然而，其作用机制仍不清楚。
本研究旨在探讨 DZXY 对慢性不可预测轻度应激（CUMS）大鼠模型的抗抑郁作用机制。
40 只雄性 SD（Sprague-Dawley）大鼠，其开放式场测试（OFT）结果相似，随机分为对照组（n=10）和实验组（n=30）。实验组采用 CUMS 法建立抑郁模型。成功建立 CUMS 模型后，将大鼠随机分为抑郁模型组和 DZXY 组。DZXY 组给予 DZXY 灌胃，抑郁模型组和对照组给予等量 0.5%羧甲基纤维素钠混悬液。连续灌胃 14 天。采用动物体重、糖水偏好试验、开放式场试验和强迫游泳试验评价 DZXY 的造模效果和抗抑郁作用。实验结束后，采集大鼠血浆，采用 UPLC/Q-TOF-MS 分析血浆代谢物变化。采用模式识别分析（pattern recognition analysis，PAR）对 UPLC/Q-TOF-MS 谱图数据进行评价，确定大鼠血浆样本中内源性代谢物的变化。
行为学研究结果表明，成功复制了抑郁大鼠模型，DZXY 具有抗抑郁作用。采用 UPLC-MS/MS 代谢组学平台，构建了偏最小二乘（PLS）和正交偏最小二乘（OPLS）的大鼠血浆代谢谱模型（R2 和 Q2≥0.5）。该模型可以区分对照组、抑郁模型组和 DZXY 组。最终，在血浆中鉴定出 38 个差异代谢物。根据 KEGG（http://www.kegg.jp）通路分析，氨基酸代谢、脂质代谢、嘌呤代谢、催乳素信号通路和胆汁分泌等代谢途径富集并代表了受影响的主要代谢途径。
本研究成功建立了 CUMS 抑郁模型。在大鼠血浆中鉴定出 38 个与抑郁相关的差异代谢物，其中 24 个被 DZXY 调节。这些结果表明，DZXY 通过调节苯丙氨酸代谢、花生四烯酸代谢、卟啉代谢、D-精氨酸和 D-鸟氨酸代谢、甾体激素生物合成、不饱和脂肪酸生物合成和甾体生物合成，可提高兴奋性，发挥抗抑郁作用。
