Background

Cancer chemotherapy-induced cognitive impairments are presumably associated with undesirable effects of chemotherapy on physiological functions of brain cells. Adaptogens are natural compounds or plant extracts increasing an organism's adaptability and survival in stress. They exhibited neuroprotective effects and increased cognitive functions in clinical studies in human beings.

Hypothesis

We hypothesized that selected adaptogenic plant extracts attenuate or prevent cancer chemotherapy-induced cognitive impairments.

Aim

We assessed the effects of selected adaptogenic herbal extracts on FEC (fixed combination 5-fluorouracil, epirubicin and cyclophosphamide) induced changes in transcriptome-wide RNA microarray profiles of neuroglia cells. The aim of the study was to predict potential effects of andrographolide, Andrographis herb, Eleutherococcus root genuine extracts, their fixed combination (AE) and the combination of Rhodiola roots, Schisandra berries and Eleutherococcus roots (RSE) on cellular and physiological, mostly cognitive functions.

Methods

Gene expression profiling was performed by transcriptome-wide mRNA microarray in the human T98G neuroglia cells after treatment with adaptogens. Interactive pathways downstream analysis was performed with data sets of significantly up- or down-regulated genes and predicted effects on cellular functions and diseases were identified by Ingenuity IPA database software.

Results

FEC deregulated 67 genes involved in decrease of neuronal development, 37 genes involved in development of the sensory system, 12 genes in extension of axons, and 3 genes in migration of neurons. Co-incubation with Andrographis paniculata (AP) suppressed FEC-induced deregulation of a large number of genes involved in predicted activation of neuronal death and inhibition of neurogenesis, and 16 genes related to inhibition of several functions in the nervous system. Co-incubation with AE suppressed FEC-induced deregulation of a number of genes involved in predicted inhibition of axon extension, migration of T98G neuroglia cells, conduction of nerves and other genes related to regulations of some other functions in the nervous system.

Conclusion

Application of cytostatic drugs in combination with apoptogenic plant extracts induced significant changes in transcriptome-wide mRNA microarray profiles of neuroglial cells. These changes indicate on potential beneficial effects on neuronal functions associated with mild cognitive impairments in cancer chemotherapy.

中文翻译：

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趋化因子中的适应原（第一部分）：植物提取物减轻癌症化疗引起的认知障碍–神经胶质细胞的转录组范围的微阵列谱

背景

癌症化学疗法诱发的认知障碍可能与化学疗法对脑细胞生理功能的不良影响有关。适应原是天然化合物或植物提取物，可提高生物体在压力下的适应性和存活率。在人类的临床研究中，它们表现出神经保护作用并增强了认知功能。

假设

我们假设选定的适应性植物提取物可减轻或预防癌症化学疗法引起的认知障碍。

目的

我们评估了对FEC（固定组合5-氟尿嘧啶，表柔比星和环磷酰胺）诱导的神经胶质细胞转录组范围的RNA微阵列谱变化的影响。这项研究的目的是预测穿心莲内酯，穿心莲药草，大肠球菌根真提取物，其固定组合（AE）以及红景天根，五味子浆果和大肠球菌根的组合（RSE）对细胞和生理功能（主要是认知功能）的潜在影响。

方法

用适应原处理后，在人类T98G神经胶质细胞中通过转录组范围的mRNA微阵列进行基因表达谱分析。利用显着上调或下调的基因数据集进行了交互式途径下游分析，并通过Ingenuity IPA数据库软件确定了对细胞功能和疾病的预测作用。

结果

FEC解除了涉及神经元发育减少的67个基因，涉及感觉系统发育的37个基因，轴突延伸的12个基因和神经元迁移的3个基因的调控。与穿心莲（AP）的共孵育抑制了FEC诱导的大量与预期的神经元死亡激活和神经发生抑制有关的基因的失调，以及与抑制神经系统若干功能相关的16个基因。与AE共同孵育可抑制FEC诱导的许多基因的失调，这些基因与预测的轴突延伸抑制，T98G神经胶质细胞迁移，神经传导以及其他与神经系统其他功能的调节有关的基因有关。

结论

细胞抑制药物与凋亡性植物提取物的组合应用诱导了神经胶质细胞转录组全mRNA基因芯片谱的显着变化。这些变化表明与癌症化疗中轻度认知障碍有关的对神经元功能的潜在有益作用。