Integrating metabolomics and network pharmacology to explore the protective effect of gross saponins of Tribulus terrestris L. fruit against ischemic stroke in rat.
Gross saponins of Tribulus terrestris L.
Metabolomics
Middle cerebral artery occlusion
Molecular docking
Network pharmacology
Journal
Journal of ethnopharmacology
ISSN: 1872-7573
Titre abrégé: J Ethnopharmacol
Pays: Ireland
ID NLM: 7903310
Informations de publication
Date de publication:
05 Dec 2020
05 Dec 2020
Historique:
received:
21
04
2020
revised:
21
06
2020
accepted:
17
07
2020
pubmed:
10
8
2020
medline:
26
2
2021
entrez:
10
8
2020
Statut:
ppublish
Résumé
Tribulus terrestris L. belongs to the family Zygophyllaceae and has been widely used as a folk medicine for a long history in Asian countries. Gross saponins of Tribulus terrestris L. fruit (GSTTF) has an obvious neuroprotective effect on the treatment of ischemic stroke, but its potential therapeutic mechanisms have not been thoroughly studied. To investigate the protective effect of GSTTF against ischemic stroke in rat. The combination of metabolomics and network pharmacology analysis was applied to investigate the protective effects of GSTTF on ischemic stroke and its putative mechanism. The related pathway of the biomarkers highlighted from metabolomics analysis was explored, then the possible targets of GSTTF were further revealed by network pharmacology analysis. Molecular docking was conducted to investigate the interaction between the active compound and target protein. Metabolomics analysis showed that metabolic disturbances were observed in serum for the rats in middle cerebral artery occlusion (MCAO). These MCAO-induced deviations in serum metabolism can be reversely changed by GSTTF via metabolic pathways regulation. Twenty-four proteins with the connectivity degree larger than 15 were selected by the network pharmacology analysis, which are considered as the possible therapeutic targets of the GSTTF against ischemic stroke. The results of molecular docking showed that the active compounds were capable of binding to the representative potential targets HSD11B1 and AR, respectively. And the docking mode of two compounds with the lowest binding energy to their target protein was illustrated by the ribbon binding map. The present study combines metabolomics and network pharmacology analysis to investigate the mechanism of MCAO-induced ischemic stroke and reveal the efficiency and possible mechanisms of GSTTF for ischemic stroke. Further studies on the bioactive saponin as well as their synergistic action on ischemic stroke will be conducted to better reveal the underlying mechanisms.
Identifiants
pubmed: 32768639
pii: S0378-8741(20)33084-1
doi: 10.1016/j.jep.2020.113202
pii:
doi:
Substances chimiques
Neuroprotective Agents
0
Saponins
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
113202Informations de copyright
Copyright © 2020 Elsevier B.V. All rights reserved.