The extract of Tribulus terrestris (TT) has been used as a component of several nutritional supplements for enhancing human vitality. However, its protective effect on ischemic stroke has yet to be fully investigated. In this study, the middle cerebral artery occlusion (MCAO) rat model was established and treated with gross saponin of TT fruit (GSTTF) by gavage to explore its anti-ischemic stroke efficacy. Liquid chromatography-mass spectrometry (LC-MS)-based metabolomics was applied to profile the brain tissue metabolite changes and further obtain the metabolic pathways that were greatly involved in the efficacy of GSTTF. Subsequent molecular biology experiments were applied to validate the findings from metabolomics analysis. The results showed that GSTTF administration remarkably decreased the infarction volume of brain tissue and improved the neurobehavioral scores of MCAO rats. Metabolomics analysis revealed that pathways, including glycerophospholipid metabolism, sphingolipid metabolism, and arachidonic acid metabolism, were considered associated with the protective effect of GSTTF against MCAO, which were greatly involved in the inflammatory responses. The results of the biochemistry analysis showed that GSTTF treatment significantly reduced the levels of TNF-α and IL-6 in brain tissue after MCAO. The anti-inflammatory mechanism of GSTTF was further investigated, which revealed that GSTTF could inhibit the TLR4/MyD88/NF-κB signaling pathway to exert protective effects on MCAO. This study provides the underlying anti-inflammatory mechanism of GSTTF for ischemic stroke protection, which has important implications for the development of GSTTF-related functional foods or food supplements.
© 2023 The Authors. Published by American Chemical Society.