Jilin Ginseng Academy, Changchun University of Chinese Medicine, Changchun, 130117, China.
School of Pharmaceutical Sciences, Changchun University of Chinese Medicine, Changchun, 130117, China; Key Laboratory of Medicinal Materials, Jilin Academy of Chinese Medicine Sciences, Changchun, 130021, China.
J Ethnopharmacol. 2021 Oct 5;278:114280. doi: 10.1016/j.jep.2021.114280. Epub 2021 Jun 1.
Gross Saponins of Tribulus terrestris L. Fruit (GSTTF) has been reported to have a protective effect against ischemic stroke, but the related mechanism is complex and still not fully investigated.
The combination of metabolomics and proteomics approach was applied to reveal the mechanisms of GSTTF in treating ischemic stroke.
The metabolite and protein changes in brain tissue were analyzed by the LC-MS-based untargeted metabolomics method and tandem mass tags (TMT)-based quantitative proteomics technology. The multivariate statistical analysis and protein-protein interaction (PPI) analysis were conducted to screen out the biomarkers, and their related pathway was further investigated by the joint pathway analysis.
A total of 110 metabolites and 359 differential proteins, which were mainly associated with complement and coagulation cascades, sphingolipid metabolism, glycerophospholipid metabolism, glutathione metabolism, and platelet activation, etc. were screened out from the rat brain tissue. The PPI network exhibited that the protein F2, Fga, Fgb, Fgg, Plg, and C3, which are greatly involved in the complement and coagulation cascades, have a relatively high connectivity degree, indicating their importance in the process of middle cerebral artery occlusion (MCAO). The GSTTF exerted a protective effect against MCAO via modulating multiple proteins on this pathway. Moreover, F2 played a key role during the protective process and worth to be further investigated due to it has been reported as one of the therapeutic targets of ischemic stroke.
The present study could improve the understanding of the potential therapeutic mechanism of GSTTF against ischemic stroke.
已报道蒺藜（Tribulus terrestris L. Fruit）总皂苷（GSTTF）具有防治缺血性中风的保护作用，但相关机制复杂，尚未完全研究清楚。
本研究采用代谢组学和蛋白质组学相结合的方法，揭示 GSTTF 治疗缺血性中风的作用机制。
采用 LC-MS 非靶向代谢组学方法和串联质量标签（TMT）定量蛋白质组学技术分析脑组织中的代谢物和蛋白质变化。采用多元统计分析和蛋白质-蛋白质相互作用（PPI）分析筛选生物标志物，并通过联合途径分析进一步研究其相关途径。
从大鼠脑组织中筛选出 110 种代谢物和 359 种差异蛋白，主要与补体和凝血级联、鞘脂代谢、甘油磷脂代谢、谷胱甘肽代谢和血小板激活等有关。PPI 网络显示，补体和凝血级联中涉及程度较大的 F2、Fga、Fgb、Fgg、Plg 和 C3 等蛋白具有较高的连接度，表明它们在大脑中动脉闭塞（MCAO）过程中具有重要作用。GSTTF 通过调节该途径上的多种蛋白质对 MCAO 发挥保护作用。此外，由于 F2 已被报道为缺血性中风的治疗靶点之一，因此它作为保护过程中的关键作用值得进一步研究。
本研究可以提高对 GSTTF 防治缺血性中风潜在治疗机制的认识。
