Blood stasis syndrome (BSS) is one of the most common symptoms of
cardiovascular diseases (CVDs) in
traditional Chinese medicine (TCM) theory. Previous studies have identified that Salvia miltiorrhiza (Danshen) has beneficial effects on BSS, but there is no relevant research from the perspective of lipidomics to study the mechanism of Danshen against BSS since
hyperlipidemia has been the widely accepted risk factor of CVDs. In this study, lipidomics technology combined with network pharmacology was applied to investigate the pathological mechanism of BSS and the protective effects of Danshen. The lipidomics profiling based on the UPLC-QTOF-MS analysis method was applied to identify the differential metabolites in the plasma of blood stasis rats. The related pathway and potential targets involved in the anti-BSS effects of Danshen were predicted by pathway analysis and network pharmacology. The biochemical results showed that Danshen intervention significantly reduced whole blood viscosity (WBV) at all the shear rates and
fibrinogen concentration (FIB) (p < 0.01) and increased activated partial thromboplastin time (APTT) effectively (p < 0.01). We also found that 52
lipid metabolites, including
glycerophospholipid,
sphingolipid, glycerolipid,
plasmalogen,
cholesterol ester, and
testosterone, were associated with blood stasis. Moreover, Dgka, Hsd17b3, Hsd3b1, Inppl1, Lpl, Pik3ca, Pik3r1, Pla2g1b, Pla2g2a, Soat1, and Soat2 were predicted as potential targets, while
glycerophospholipid metabolism, glycerolipid metabolism,
steroid and
steroid hormone biosynthesis,
phosphatidylinositol signaling system, and
ether lipid metabolism were involved as shared critical pathways of lipidomics analysis and network pharmacology. Collectively, this study offered a new understanding of the protection mechanism of Danshen against BSS, which provided new insight to explore the protective effects of Danshen.