Cerebral metabonomics study on Parkinson's disease mice treated with extract of Acanthopanax senticosus harms
Cerebral metabonomics study on Parkinson's disease mice treated with extract of Acanthopanax senticosus harms
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DOI：
10.1016/j.phymed.2013.06.002
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发表时间：
2013-10-15
期刊：
影响因子：
7.9
通讯作者：
Liu, Shu-min
中科院分区：
文献类型：
--
作者：
Li, Xu-zhao;Zhang, Shuai-nan;Liu, Shu-min
刺五加提取物（EAS）对帕金森病（PD）小鼠多巴胺能神经元损伤具有神经保护作用。然而，其抗PD机制的研究是具有挑战性的，由于PD的病理生理学复杂，EAS的复杂性与多种成分作用于不同的代谢途径。在这里，我们研究了EAS治疗后MPTP诱导的PD小鼠模型的代谢特征和潜在的生物标志物。采用超高效液相色谱-四极杆飞行时间质谱联用技术（UPLC-QTOF-MS）对1-甲基-4-苯基-1，2，3，6-四氢吡啶盐酸盐（MPTP-HCl）诱导的PD小鼠模型进行代谢指纹图谱分析。通过偏最小二乘判别分析（PLS-DA），观察到由MPTP引起的代谢紊乱在EAS处理后得到恢复。MPTP诱导的代谢产物包括L-多巴、5 '-甲硫腺苷、十四酰肉毒碱、植物鞘氨醇-1-P、Cer（d18：0/18：0）、LysoPC（20：4（5 Z，8 Z，11 Z，14 Z））、L-棕榈酰肉毒碱、二十四酰甘氨酸、morphiceptin和硬脂酰肉毒碱，这些代谢产物的变化显著，是参与PD发病机制的潜在生物标志物。除Cer（d18：0/18：0）、LysoPC（20：4（5 Z，8 Z，11 Z，14 Z））、morphiceptin外，其他生物标志物的衍生均能被EAS调节。EAS对PD的治疗作用可能与调节酪氨酸代谢、线粒体长链饱和脂肪酸β-氧化、脂肪酸代谢、蛋氨酸代谢和鞘脂代谢有关。本研究表明，EAS确实可以恢复代谢产物的变化，EAS的治疗可能与相关代谢途径的调节有关。(C)2013 Elsevier GmbH. All rights reserved.
Extract of Acanthopanax senticosus harms (EAS) has neuroprotective effect on Parkinson's disease (PD) mice against dopaminergic neuronal damage. However, studies of its anti-PD mechanism are challenging, owing to the complex pathophysiology of PD, and complexity of EAS with multiple constituents acting on different metabolic pathways. Here, we have investigated the metabolic profiles and potential biomarkers in a mice model of MPTP-induced PD after treatment of EAS. Metabonomics based on ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) was used to profile the metabolic fingerprints of mesencephalon obtained from 1-Methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine Hydrochloride (MPTP-HCl)-induced PD mice model with and without EAS treatment. Through partial least squares-discriminate analysis (PLS-DA), it was observed that metabolic perturbations induced by MPTP were restored after treatment with EAS. Metabolites with significant changes induced by MPTP, including L-dopa, 5'-methylthioadenosine, tetradecanoyl-carnitine, phytosphingosine-1-P, Cer(d18:0/18:0), LysoPC(20:4(5Z,8Z,11Z,14Z)), L-palmitoyl -carnitine, tetracosanoylglycine, morphiceptin and stearoylcarnitine, were characterized as potential biomarkers involved in the pathogenesis of PD. The derivations of all those biomarkers can-be regulated by EAS treatment except Cer(d18:0/18:0), LysoPC(20:4(5Z,8Z,11Z,14Z)), morphiceptin. The therapeutic effect of EAS on PD may involve in regulating the tyrosine metabolism, mitochondrial beta-oxidation of long chain saturated fatty acids, fatty acid metabolism, methionine metabolism, and sphingolipid metabolism. This study indicated that changed metabolites can be certainly recovered by EAS, and the treatment of EAS can be connected with the regulation of related metabolic pathways. (C) 2013 Elsevier GmbH. All rights reserved.