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Investigating the Protective Effect of Gross Saponins of Tribulus terrestris Fruit against Ischemic Stroke in Rat Using Metabolomics and Network Pharmacology

1
Jilin Ginseng Academy, Changchun University of Chinese Medicine, Changchun 130117, China
2
School of Pharmaceutical Sciences, Changchun University of Chinese Medicine, Changchun 130117, China
3
Key Laboratory of Medicinal Materials, Jilin Academy of Chinese Medicine Sciences, Changchun 130021, China
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Metabolites 2019, 9(10), 240; https://doi.org/10.3390/metabo9100240
Received: 12 September 2019 / Revised: 11 October 2019 / Accepted: 19 October 2019 / Published: 21 October 2019
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. View Full-Text
Keywords: ischemic stroke; gross saponins of Tribulus terrestris; LC-MS-based metabolomics; network pharmacology ischemic stroke; gross saponins of Tribulus terrestris; LC-MS-based metabolomics; network pharmacology
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Wang, Y.; Guo, W.; Liu, Y.; Wang, J.; Fan, M.; Zhao, H.; Xie, S.; Xu, Y. Investigating the Protective Effect of Gross Saponins of Tribulus terrestris Fruit against Ischemic Stroke in Rat Using Metabolomics and Network Pharmacology. Metabolites 2019, 9, 240.

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