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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.

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.

SUBMITTER: Wang Y

PROVIDER: S-EPMC6835270 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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

Wang Yang Y Guo Wenjun W Liu Yue Y Wang Jifeng J Fan Meiling M Zhao Hongyu H Xie Shengxu S Xu Yajuan Y

Metabolites 20191021 10

Stroke is one of the leading causes of death and long-term disability worldwide. Gross saponins of <i>Tribulus terrestris</i> 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 ...[more]

PMID: 31640179

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Project description:BackgroundTo investigate the protective effect of ultrasound microbubble combined with gross saponins of tribulus terrestris (GSTT) (a Chinese herb) on glaucomatous optic nerve damage.MethodsRabbits were randomly divided into five groups. Normal (Group A), high intraocular pressure (IOP, Group B), GSTT (Group C), GSTT + ultrasound (Group D), and GSTT + ultrasound + microbubble destruction (Group E). The high intraocular pressure eye (model eye) was compared to the normal eye (control eye) at 1, 2, and 4 weeks after model establishment. Rabbits were sacrificed 4 weeks later to measure the retina thickness using Cirrus OCT, slit lamp photograph, and fundus photography. The retina and optic nerve of rabbits in each group were collected and the stretched retina were prepared for retinal ganglion cell (RGC) counting, the optic nerve axon was measured, and a transmission electron microscopy was used.ResultsRetina thickness based on Cirrus OCT: mean retinal thickness in Group E was significantly greater than that in Group B, but still thinner than that in Group A. RGCs counts: RGCs counts in Group E were significantly higher than those in Groups B, C, and D but still lower than those in Group A. Quantitative analysis of optic nerve axons: In Group E, the number of optic nerves was increased, diameters of optic nerve axons were decreased, the percentage of optic nerve area occupied by axons was increased, and there were statistically significant differences compared to Groups B, C, and D. Content of GSTT in retina: The content of GSTT in Group E was significantly higher than that in other groups. Observation of the rabbit optic nerves: In Group E, the structure of the myelin sheath of the optic nerve was still intact but less ordered, and the microtubule and microfilament structures in the axons were clear.ConclusionsCombination of the ultrasound microbubble and GSTT can improve the protective effect of GSTT on optic nerve damage in rabbits with ocular hypertension.

Project description:BackgroundTribulus terrestris L. (TT) is one of the most common Chinese herbs and distributes in various regions in China. TT was first documented to treat breast cancer in Shen-Nong-Ben-Cao-Jing. However, the pharmacological activities of TT extract on liver cancer have not been reported. In this study, we investigated its anti-liver cancer activity and underlying mechanism.MethodsTraditional Chinese Medicine Systems Pharmacology (TCMSP) and PharmMapper databases were used to obtain the active ingredients and the targets of TT. Genecards database was employed to acquire TT targets in liver cancer. Furthermore, Venny 2.1, Cytoscape 3.8.2, DAVID 6.8 software were utilized to analyze the relationship between TT and liver cancer. In vivo experiment: The animal model of liver cancer was established by injection of H22 cells into Balb/c mice. After five days, drugs were intragastrically administered to the mice daily for 10 days. Body weight, tumor size and tumor weight were recorded. Tumor inhibitory rate was calculated. Protein levels were examined by Western blotting. Pathological changes of liver cancer tissues were evaluated by HE and Tunel staining. Metabolomics study: LC-MS was used to analyze different metabolites between model and TTM groups.Results12 active ingredients of TT, 127 targets of active ingredients, 17,378 targets of liver cancer, and 125 overlapping genes were obtained. And then, 118 items of GO biological processes (BP), 54 items of GO molecular function (MF), 35 items of GO cellular component (CC) and 128 pathways of KEGG were gotten (P < 0.05). Moreover, 47 differential metabolites were affirmed and 66 pathways of KEGG (P < 0.05) were obtained. In addition, after TT and sorafenib treatment, tumor size was markedly reduced, respectively, compared with model group. Tumor weight was significantly decreased and tumor inhibitory rate was more than 44% in TTM group. After TT treatment, many adipocytes, cracks between tumor cells and apoptosis were found. The levels of pro-Cathepsin B, Cathepsin B, Bax, Bax/Bcl2, Caspase3 and Caspase7 were markedly increased, but the level of Bcl2 was significantly reduced after TT treatment.ConclusionTT has a broad range of effects on various signaling pathways and biological processes, including the regulation of apoptosis. It exhibits antitumor activity in an animal model of liver cancer and activates the apoptotic pathway by decreasing Sph level. This study provides valuable information regarding the potential use of TT extract in the treatment of liver cancer and highlights the importance of investigating the underlying molecular mechanisms of traditional medicines for the development of new therapeutic drugs in liver cancer.

Dataset Information

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

Publications

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

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