Gao Jian, Yang Hongjun, Chen Jianxin, Fang Jiansong, Chen Chang, Liang Rixin, Yang Gengliang, Wu Hongwei, Wu Chuanhong, Li Shaojing
Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, PR China.
Mol Biosyst. 2013 Sep;9(9):2311-21. doi: 10.1039/c3mb70040b.
Ischemic stroke, a devastating disease with a complex pathophysiology, is a leading cause of death and disability worldwide. In our previous study, we reported that galangin provided direct protection against ischemic injury and acted as a potential neuroprotective agent. However, its associated neuroprotective mechanism has not yet been clarified. In this paper, we explored the potential AA biomarkers in the acute phase of cerebral ischemia and the effect of galangin on those potential biomarkers. In our study, 12 AAs were quantified in rat serum and found to be impaired by middle cerebral artery occlusion (MCAO)-induced focal cerebral ischemia. Using partial least squares discriminate analysis (PLS-DA), we identified the following amino acids as potential biomarkers of cerebral ischemia: glutamic acid (Glu), homocysteine (Hcy), methionine (Met), tryptophan (Trp), aspartic acid (Asp), alanine (Ala) and tyrosine (Tyr). Moreover, four amino acids (Hcy, Met, Glu and Trp) showed significant change in galangin-treated (100 and 50 mg kg(-1)) groups compared to vehicle groups. Furthermore, we identified three pathway-related enzymes tyrosine aminotransferase (TAT), glutamine synthetase (GLUL) and monocarboxylate transporter (SLC16A10) by multiplex interactions with Glu and Hcy, which have been previously reported to be closely related to cerebral ischemia. Through an analysis of the metabolite-protein network analysis, we identified 16 proteins that were associated with two amino acids by multiple interactions with three enzymes; five of them may become potential biomarkers of galangin for acute ischemic stroke as the result of molecule docking. Our results may help develop novel strategies to explore the mechanism of cerebral ischemia, discover potential targets for drug candidates and elucidate the related regulatory signal network.
缺血性中风是一种具有复杂病理生理学的毁灭性疾病，是全球范围内死亡和残疾的主要原因。在我们之前的研究中，我们报道了高良姜素可对缺血性损伤提供直接保护，并作为一种潜在的神经保护剂发挥作用。然而，其相关的神经保护机制尚未阐明。在本文中，我们探讨了脑缺血急性期潜在的氨基酸生物标志物以及高良姜素对这些潜在生物标志物的影响。在我们的研究中，对大鼠血清中的12种氨基酸进行了定量分析，发现它们因大脑中动脉闭塞（MCAO）诱导的局灶性脑缺血而受损。使用偏最小二乘判别分析（PLS-DA），我们确定了以下氨基酸作为脑缺血的潜在生物标志物：谷氨酸（Glu）、同型半胱氨酸（Hcy）、蛋氨酸（Met）、色氨酸（Trp）、天冬氨酸（Asp）、丙氨酸（Ala）和酪氨酸（Tyr）。此外，与溶剂对照组相比，在高良姜素治疗组（100和50 mg kg(-1)）中，四种氨基酸（Hcy、Met、Glu和Trp）显示出显著变化。此外，我们通过与Glu和Hcy的多重相互作用鉴定了三种与途径相关的酶，即酪氨酸转氨酶（TAT）、谷氨酰胺合成酶（GLUL）和单羧酸转运体（SLC16A10），此前已报道它们与脑缺血密切相关。通过代谢物-蛋白质网络分析，我们鉴定了16种通过与三种酶的多重相互作用与两种氨基酸相关的蛋白质；其中五种可能因分子对接而成为高良姜素治疗急性缺血性中风的潜在生物标志物。我们的结果可能有助于开发新的策略来探索脑缺血的机制，发现候选药物的潜在靶点，并阐明相关的调节信号网络。
