Investigating the in vivo effect of Tribulus terrestris extract in MCAO rats by using LC-MS-based metabolomics combined with the molecular docking.

Tribulus terrestris L. fruit (TT) is a traditional Chinese herbal medicine and has been used to treat ischemic stroke (IS). This study aimed to investigate the protective effect of TT extract, named TT15, on middle cerebral artery occlusion (MCAO) rats by metabolomics and molecular docking, and find the targets of action and the material basis of TT15 against IS. The results of the infarct volume and neurological defect scores confirmed the efficacy of TT15. The serum metabolomics analysis using LC-MS revealed that Model group animals experienced a variety of metabolic disturbances when compared to the Sham group. TT15 can restore the MCAO-induced serum metabolite changes by modulating multiple metabolic pathways. Six enzymes were highlighted by the metabolite-reaction-enzyme-gene (M-R-E-G) network analysis, which might be the possible targets for the TT15 against IS. Molecular docking analysis was applied to show binding affinities between active compounds and these enzymes. The representative docking mode with the lowest binding energy between three compounds and phospholipase A 2 (PLA2) and peroxidase (POD), respectively, were displayed by the ribbon binding map. This study profiles the metabolic changes of MCAO-induced IS and investigates the efficacy and the corresponding mechanism of TT15 in the treatment of IS.