Stroke is one of the most common neurological disorders and seriously threatens human life. Gross saponins of Tribulus terrestris fruit (GSTTF) are used for neuroprotective treatment on convalescents of ischemic stroke. However, the therapeutic effects and mechanisms have not yet well understood, especially from the metabolic perspective. In this study, the protective effect of GSTTF on ischemic stroke in a middle cerebral artery occlusion (MCAO) rat model was investigated by the GC-MS-based metabolomics approach. 2,3,5-triphenyltetrazolium chloride (TTC) staining of brain tissues showed that GSTTF significantly reduced the infarct area after MCAO surgery. Metabolomic profiling showed a series of metabolic perturbation occurs in ischemic stroke compared with sham group. GSTTF can reverse the MCAO-induced serum metabolic deviations by regulating multiple metabolic pathways including fatty acids metabolism, amino acids metabolism, and carbohydrates metabolism. The current study provided a useful approach for understanding the mechanism of MCAO-induced ischemic stroke and a reliable basis for evaluating the efficacy of GSTTF in the treatment of ischemic stroke.

Stroke is one of the leading causes of death and long-term disability worldwide. Gross saponins of Tribulus terrestris fruit (GSTTF) has been used for neuroprotective therapy on convalescents of ischemic stroke. But the related therapeutic mechanisms have not yet been well investigated. This study aimed to investigate the protective effects of GSTTF on ischemic stroke using metabolomics coupled with network pharmacology analysis. The rat urine sample was collected and profiled by an LC-MS-based metabolomics approach. The pathway analysis was performed based on the highlighted biomarkers, then the network pharmacology approach was applied to screen the potential therapeutic targets of GSTTF. Metabolomics analysis showed that a series of metabolic perturbations occurred in the middle cerebral artery occlusion (MCAO) group compared with the sham group. Gross saponins of Tribulus terrestris fruit can change the MCAO-induced urine metabolic deviations in a reverse manner via regulating multiple metabolic pathways. Two proteins, inducible nitric oxide synthase (NOS2) and glycogen synthase kinase-3 beta (GSK3B), were highlighted by the network pharmacology analysis, which may be the potential therapeutic targets for the GSTTF against ischemic stroke. This study provides an overview of the mechanism of MCAO-induced ischemic stroke and investigates the efficacy of GSTTF in the treatment of ischemic stroke. Further study is needed to reveal its underlying mechanisms more clearly.

Aging affects the brain function in elderly individuals, and Dushen Tang (DST) is widely used for the treatment of senile diseases. In this study, the protective effect of DST against memory impairment was evaluated through the Morris water maze (MWM) test and transmission electron microscopy (TEM). A joint analysis was also performed using LC‐MS metabolomics and the microbiome. The MWM test showed that DST could significantly improve the spatial memory and learning abilities of rats with memory impairment, and the TEM analysis showed that DST could reduce neuronal damage in the hippocampus of rats with memory impairment. Ten potential biomarkers involving pyruvate metabolism, the synthesis and degradation of ketone bodies, and other metabolic pathways were identified by the metabolomic analysis, and it was found that 3‐hydroxybutyric acid and lactic acid were involved in the activation of cAMP signaling pathways. The 16S rDNA sequencing results showed that DST could regulate the structure of the gut microbiota in rats with memory impairment, and these effects were manifested as changes in energy metabolism. These findings suggest that DST exerts a good therapeutic effect on rats with memory impairment and that this effect might be mainly achieved by improving energy metabolism. These findings might lead to the potential development of DST as a drug for the treatment of rats with memory impairment.