As the greatest medical and socioeconomic problem in developing countries, stroke is the second or third leading cause of death in China and worldwide. In adult organisms suffering from stroke, transplanted stem cell has the ability to repair damaged tissues by regenerating autologous cells, while ginsenoside Rg1 could promote proliferation and differentiation of stem cells. Although obvious anti-stroke effects of ginsenoside Rg1 and transplanted stem cells have been verified in publications, the mechanism exploration remained challenging. Our study was carried out to investigate the synergistic effects of ginsenoside Rg1 and neural stem cell (NSC) transplantation on MCAO rats with a 1H NMR-based non-targeted metabolomics methods to identify potential biomarkers and protein targets and discover the potential mechanism. NSCs transplantation after MCAO combined with ginsenoside Rg1 administration could significantly improve the cerebral infract and neurological deficits. The treatment significant intervened the levels of ten metabolites, and perturbed energy metabolism, amino acids metabolism and lipids metabolism. And 11 enzymes were identified and verified as the targets of NSCs transplantation and ginsenoside Rg1 administration on MCAO rats. Our findings helped to improve the anti-stroke mechanism of NSCs transplantation and ginsenoside Rg1 and supply a theory basis for the combined research of stem cell and Chinese medicine in future.

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