Research Center of Basic Integrative Medicine, School of Basic Medical Science, Guangzhou University of Chinese Medicine, Guangzhou 510006, China.
Key Laboratory of Depression Animal Model Based on TCM Syndrome, Key Laboratory of TCM for Prevention and Treatment of Brain Diseases with Cognitive Dysfunction, Jiangxi University of Chinese Medicine, Nanchang 330004, China.
Int J Mol Sci. 2023 Feb 9;24(4):3485. doi: 10.3390/ijms24043485.
Cognitive deficiency is one of the fundamental characteristics of late-onset depression (LOD). Luteolin (LUT) possesses antidepressant, anti-aging, and neuroprotective properties, which can dramatically enhance cognition. The altered composition of cerebrospinal fluid (CSF), which is involved in neuronal plasticity and neurogenesis, directly reflects the physio-pathological status of the central nervous system. It is not well known whether the effect of LUT on LOD is in association with a changed CSF composition. Therefore, this study first established a rat model of LOD and then tested the therapeutic effects of LUT using several behavioral approaches. A gene set enrichment analysis (GSEA) was used to evaluate the CSF proteomics data for KEGG pathway enrichment and Gene Ontology annotation. We combined network pharmacology and differentially expressed proteins to screen for key GSEA-KEGG pathways as well as potential targets for LUT therapy for LOD. Molecular docking was adopted to verify the affinity and binding activity of LUT to these potential targets. The outcomes demonstrated that LUT improved the cognitive and depression-like behaviors in LOD rats. LUT may exert therapeutic effects on LOD through the axon guidance pathway. Five axon guidance molecules-, , , , and -as well as , , and , may be candidates for the LUT treatment of LOD.
认知缺陷是迟发性抑郁症（LOD）的基本特征之一。木犀草素（LUT）具有抗抑郁、抗衰老和神经保护作用，可以显著改善认知功能。脑脊液（CSF）组成的改变与神经元可塑性和神经发生有关，直接反映中枢神经系统的生理病理状态。目前尚不清楚 LUT 对 LOD 的作用是否与 CSF 组成的改变有关。因此，本研究首先建立了 LOD 大鼠模型，然后使用多种行为方法测试了 LUT 的治疗效果。采用基因集富集分析（GSEA）对 CSF 蛋白质组学数据进行 KEGG 通路富集和基因本体论注释评估。我们结合网络药理学和差异表达蛋白筛选出关键的 GSEA-KEGG 通路以及 LUT 治疗 LOD 的潜在靶点。采用分子对接验证 LUT 与这些潜在靶点的亲和力和结合活性。结果表明，LUT 改善了 LOD 大鼠的认知和抑郁样行为。LUT 可能通过轴突导向途径对 LOD 发挥治疗作用。五种轴突导向分子、、、、和——以及、和——可能是 LUT 治疗 LOD 的候选药物。
