Multi-omics analysis of brain tissue metabolome and proteome reveals the protective effect of gross saponins of Tribulus terrestris L. fruit against ischemic stroke in rat

Abstract

Ethnopharmacological relevanceGross 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. Aim of the studyThe combination of metabolomics and proteomics approach was applied to reveal the mechanisms of GSTTF in treating ischemic stroke. Materials and methodsThe 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. ResultsA 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. ConclusionThe present study could improve the understanding of the potential therapeutic mechanism of GSTTF against ischemic stroke.