The Synergistic Mechanism of Total Saponins and Flavonoids in Notoginseng–Safflower against Myocardial Infarction Using a Comprehensive Metabolomics Strategy

Notoginseng and safflower are commonly used traditional Chinese medicines for benefiting qi and activating blood circulation. A previous study by our group showed that the compatibility of the effective components of total saponins of notoginseng (NS) and total flavonoids of safflower (SF), named NS–SF, had a preventive effect on isoproterenol (ISO)-induced myocardial infarction (MI) in rats. However, the therapeutic effect on MI and the synergistic mechanism of NS–SF are still unclear. Therefore, integrated metabolomics, combined with immunohistochemistry and other pharmacological methods, was used to systematically research the therapeutic effect of NS–SF on MI rats and the synergistic mechanism of NS and SF. Compared to NS and SF, the results demonstrated that NS–SF exhibited a significantly better role in ameliorating myocardial damage, apoptosis, easing oxidative stress and anti-inflammation. NS–SF showed a more significant regulatory effect on metabolites involved in sphingolipid metabolism, glycine, serine, and threonine metabolism, primary bile acid biosynthesis, aminoacyl-tRNA biosynthesis, and tricarboxylic acid cycle, such as sphingosine, lysophosphatidylcholine (18:0), lysophosphatidylethanolamine (22:5/0:0), chenodeoxycholic acid, L-valine, glycine, and succinate, than NS or SF alone, indicating that NS and SF produced a synergistic effect on the treatment of MI. This study will provide a theoretical basis for the clinical development of NS–SF