Abstract
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.
Highlights
Stroke is one of the leading causes of death and long-term disability worldwide
A remarkable infarct area in the coronal brain sections was yielded after middle cerebral artery occlusion (MCAO) surgery, which is consistent with their highest neurological defect score among three groups
The results indicate that the administration of Gross saponins of Tribulus terrestris fruit (GSTTF) prior to MCAO
Summary
Stroke is one of the leading causes of death and long-term disability worldwide. The origin of over80% of all strokes are ischemic events, which can result in harmful neurological sequelae accompanied by severe morphological and molecular alterations [1,2]. As stated by the World Health Organization (https://www.who.int/topics/cerebrovascular_accident/en/), ischemic stroke is caused by the interruption of the blood supply to the brain when a blood vessel bursts or is blocked by a clot, which can cut off the supply of oxygen and nutrients bringing damage to the brain tissue. Thrombolysis is considered as the first-choice treatment for ischemic stroke, which tries to dissolve the Metabolites 2019, 9, 240; doi:10.3390/metabo9100240 www.mdpi.com/journal/metabolites. The mechanisms and methods for a precise pathology of ischemic brain injury have not yet matured; there are no generally accepted and effective treatments for ischemic stroke to date [3,4]. Traditional Chinese herbal medicine (TCHM) has shown unique therapeutic effects for various diseases and disorders with the advantages of little side effects and low cost.
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