Abstract
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.
Highlights
Cardiovascular diseases (CVDs) are a leading cause of death for adults and remain a significant cause of health loss in all regions of the world [1, 2]. e earlier study has stated that 85.8% of 324 patients with CVDs had blood stasis syndrome (BSS) [3]
Compared with the control group, all the shear rates of the whole blood viscosity (WBV) levels in the model group were significantly increased (p < 0.01), which indicated that the acute blood stasis (ABS) rat models were successfully established. e WBV at all the shear rates was significantly reduced (p < 0.01) in the positive control group compared to the model group
E effects of Danshen on blood coagulation function were measured by assessing of prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen concentration (FIB), and thrombin time (TT) levels in the plasma
Summary
Cardiovascular diseases (CVDs) are a leading cause of death for adults and remain a significant cause of health loss in all regions of the world [1, 2]. e earlier study has stated that 85.8% of 324 patients with CVDs had blood stasis syndrome (BSS) [3]. Cardiovascular diseases (CVDs) are a leading cause of death for adults and remain a significant cause of health loss in all regions of the world [1, 2]. E earlier study has stated that 85.8% of 324 patients with CVDs had blood stasis syndrome (BSS) [3]. One of the most common traditional Chinese medicine (TCM) terminologies in cardiovascular diseases, is a significant symptom of patients with CVDs [4]. Modern medical researches reveal that pathological changes associated with blood stasis syndrome, including inflammation, thrombosis, and tissue edema, are caused by ischemia, hypoxia of tissue organs, blood viscosity abnormalities, and circulation disorders [6]. Literature shows that, in the metabolomics analysis of rats with blood stasis, the fluctuations of endogenous metabolites may be responsible for this disease [8, 9]. The underlying lipid metabolic mechanism and identification of potential lipid biomarkers remain equivocal
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