BACKGROUD: Draconis Sanguis (DS), a precious traditional Chinese medicine for activating blood and dissolving stasis, has been used in treating ischemic cardiovascular diseases. However, the underlying mechanism of DS against heart failure after myocardial ischemia (MI) remains unclear, especially concerning angiogenesis and energy metabolism, which have never been elucidated. PURPOSE: This study aimed to explore the protective mechanism of DS in ischemic heart failure (IHF) from the perspectives of angiogenesis and energy metabolism. METHODS: We investigated the effects of DS on an in vivo model of IHF induced by ligation of the left anterior descending coronary artery (LADCA) and an in vitro model of HUVECs injury induced by hypoxia. High-performance liquid chromatography (HPLC) was performed to identify components of DS. Echocardiography, histopathology, and cardiac enzymes analysis were used to examine the anti-ischemic heart failure effect of DS. Transcriptome sequencing, positron emission tomography (PET), HPLC, and chocardiography were performed on heart tissues to explore the underlying mechanism. Furthermore, the relevant targets were investigated by real-time quantitative PCR (RT-qPCR), Western blotting, immunohistochemistry, and immunofluorescence. Finally, potential pharmacodynamic substances were identified with a cell model and molecular docking. RESULTS: The results showed DS increased survival of rats with IHF for 28 days by 10 %, significantly ameliorated cardiac function in rats with IHF, increased left ventricular ejection fraction by 20 %, and it reduced pathological changes and cardiac enzymes levels. These results indicated that DS alleviated myocardial ischaemia injury. The effects described above were related to the regulation of the HIF-1α/VEGF signallings pathway to promote angiogenesis in the ischemic myocardium, increase the local oxygen supply and optimize myocardial energy metabolism "promoting lipid and inhibiting glucose" and increasing local ATP production. Moreover, DS compounds were identified
these compounds protected HUVECs from hypoxia and glucose deprivation, significantly upregulated HIF-1α gene expression, and were shown to be related to this mechanism in vitro experiments. CONCLUSIONS: DS ameliorates cardiac function by optimizing myocardial energy metabolism after promoting angiogenesis via HIF-1α/VEGF signalling pathway regulation.