UHPLC-QTOF/MS-based metabolomics investigation for the protective mechanism of Danshen in Alzheimer's disease cell model induced by A1-42
UHPLC-QTOF/MS-based metabolomics investigation for the protective mechanism of Danshen in Alzheimer's disease cell model induced by A1-42
复制标题
基于UHPLC-QTOF/MS的代谢组学研究丹参对A(1-42)诱导的阿尔茨海默病细胞模型的保护机制
DOI：
10.1007/s11306-019-1473-x
复制
发表时间：
2019-02-01
期刊：
影响因子：
3.6
通讯作者：
Chai, Yifeng
中科院分区：
文献类型：
--
作者：
Zhang, Mingyong;Liu, Yue;Chai, Yifeng
阿尔茨海默病（Alzheimer's disease，AD）是一种慢性神经退行性疾病，目前尚无明确的发病机制和有效的治疗方法。丹参，丹参的干燥根和根茎，被广泛用于阿尔茨海默病的治疗，以改善症状，目的研究AD的潜在生物标志物，阐明丹参对AD细胞模型的保护作用机制。本文建立了一种基于超高效液相色谱-定量飞行/质谱（UHPLC-QTOF/MS）结合偏最小二乘判别分析（PLS-DA）的方法，用于区分人脑微血管内皮细胞（hBMEC）和淀粉样蛋白（A（1-42））诱导的AD细胞模型之间的代谢改变。为了进一步阐明AD的病理生理，相关的代谢途径进行了研究。Results 33个不同的潜在生物标志物被筛选出来，并被认为是潜在的生物标志物对应于AD，其中大部分改善，部分恢复正常，在丹参预保护组。发现AD与精氨酸和脯氨酸代谢紊乱、谷胱甘肽代谢紊乱、丙氨酸天冬氨酸和谷氨酸代谢紊乱、组氨酸代谢紊乱、泛酸和CoA生物合成紊乱、苯丙氨酸酪氨酸和色氨酸生物合成紊乱、柠檬酸循环紊乱和甘油磷脂代谢紊乱密切相关。丹参对AD细胞模型的保护机制可能与部分调节被干扰的信号通路有关。为丹参治疗AD的作用机制研究提供了依据，这一研究方法可推广到其他中药及疾病的作用机制研究。
IntroductionAlzheimer's disease (AD) is a chronic neurodegenerative disorder with neither definitive pathogenesis nor effective therapy so far. Danshen, the dried root and rhizome of Salvia miltiorrhiza Bunge, is used extensively in Alzheimer's disease treatment to ameliorate the symptoms, but the underlying mechanism remains to be clarified.ObjectivesTo investigate potential biomarkers for AD and elucidate the protective mechanism of Danshen on AD cell model.MethodsAn ultra high performance liquid chromatography-quadrupole time of flight mass spectrometry (UHPLC-QTOF/MS)-based approach combined with partial least squares discriminant analysis (PLS-DA) has been developed to discriminate the metabolic modifications between human brain microvascular endothelial cell (hBMEC) and AD cell model induced by amyloid- protein (A(1-42)). To further elucidate the pathophysiology of AD, related metabolic pathways have been studied.ResultsThirty-three distinct potential biomarkers were screened out and considered as potential biomarkers corresponding to AD, which were mostly improved and partially restored back to normalcy in Danshen pre-protection group. It was found that AD was closely related to disturbed arginine and proline metabolism, glutathione metabolism, alanine aspartate and glutamate metabolism, histidine metabolism, pantothenate and CoA biosynthesis, phenylalanine tyrosine and tryptophan biosynthesis, citrate cycle and glycerophospholipid metabolism, and the protective mechanism of Danshen in AD cell model may be related to partially regulating the perturbed pathways.ConclusionsThese outcomes provide valuable evidences for therapeutic mechanism investigation of Danshen in AD treatment, and such an approach could be transferred to unravel the mechanism of other traditional Chinese medicine (TCM) and diseases.