Metabolomic evidence for the therapeutic effect of gentiopicroside in a corticosterone-induced model of depression.
Metabolomic evidence for the therapeutic effect of gentiopicroside in a corticosterone-induced model of depression.
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DOI：
10.1016/j.biopha.2019.109549
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发表时间：
2019-12
期刊：
影响因子：
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通讯作者：
Tao Yao;Qin Cui;Zhichao Liu;C. Wang;Qi Zhang;Gaohua Wang
中科院分区：
文献类型：
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作者：
Tao Yao;Qin Cui;Zhichao Liu;C. Wang;Qi Zhang;Gaohua Wang
背景抑郁症是一种严重威胁人类生活质量的疾病。为探讨龙胆苦苷对抑郁症的治疗作用，本研究采用代谢组学方法研究了龙胆苦苷对皮质酮诱导的抑郁症的治疗作用。方法将36只大鼠随机分为3组：正常组、模型组（抑郁症）和治疗组（抑郁症+龙胆苦苷）。给予皮质酮诱导抑郁样模型大鼠。采用Morris水迷宫实验验证大鼠的行为学表现。取大鼠海马进行代谢组学检测。提取组间差异表达的代谢产物用于热图、Go和途径富集分析。结果皮质酮可损伤大鼠学习记忆能力，降低5-HT水平，龙胆苦苷可逆转皮质酮对学习记忆能力的影响。对从三组大鼠海马中获得的代谢产物进行主成分分析（PCA）。GO和途径富集分析揭示了神经元鞘脂代谢等的参与。龙胆苦苷能抑制皮质酮诱导的细胞凋亡，并能降低神经元细胞增殖和BDNF水平。花生四烯酸（ARA）可逆转龙胆苦苷对神经元cells.ConclusionThese结果表明，龙胆苦苷通过调节代谢产物，减少抑郁动物海马细胞凋亡，促进海马细胞增殖。此外，我们的研究为抑郁症的临床治疗提供了新的依据，并证明了龙胆苦苷在这一病理领域的潜在疗效。
BackgroundDepression is a disease that seriously threatens the quality of human life. To explore the effect of gentiopicroside on depression, this study investigated the therapeutic effect of gentiopicroside on corticosterone-induced depressionin vivoandin vitroby using metabolomic methods.MethodsA total of 36 rats were randomly assigned to three groups: a normal group, model group (depression), and treatment group (depression + gentiopicroside). Corticosterone was administrated to induce depression-like model rats. Morris water maze test was used to validated the behavior performance. The hippocampus of rats was obtained for metabolomic detection. Metabolites that were differentially expressed between the groups were extracted for Heatmap, Go, and pathway enrichment analyses. Finally, neuronal cells were cultured and examined to validated the effect of gentiopicroside.ResultsCorticosterone injured rats learning capacity, and decreased the levels of 5-HT, and reversed by gentiopicroside delivery. Metabolites obtained from the hippocampus of rats in the three groups were subjected to a principal component analysis (PCA). Go and pathway enrichment analyses revealed the involvement of sphingolipid metabolism et al. Gentiopicroside could inhibit apoptosis caused by corticosterone, and also decrease neuronal cell proliferation and BDNF levelsin vitro. Arachidonic acid (ARA) reversed the protective effect of gentiopicroside on neuronal cells.ConclusionThese findings suggest that gentiopicroside reduces apoptosis and increases the proliferation of hippocampus cells in depressed animals by regulating metabolites. Moreover, our study provides a new basis for the clinical treatment of depression and demonstrates the potential efficacy of gentiopicroside in this area of pathology.