Myocardial Lipidomics Revealed Glycerophospholipid and Sphingolipid Metabolism as Therapeutic Targets of Qifu Decoction Against Heart Failure

ABSTRACT Qifu decoction (QFD) has shown potential benefits in treating heart failure. However, the potential mechanism of QFD remains unclear. In this study, myocardial lipidomics, based on ultra‐high‐performance liquid chromatography coupled with an electrospray ionization hybrid quadrupole Orbitrap mass spectrometry (UPLC‐ESI‐Q‐Exactive/MS), was employed to identify potential therapeutic targets of QFD for treating heart failure in a mice model induced by ligating the left anterior descending coronary artery. It was found that 47 lipid metabolites were associated with heart failure, of which 35 showed a significant reversal during QFD treatment. The QFD‐reversed lipid metabolites were mainly located on phosphatidylcholine, lysophosphatidylcholine, sphingomyelin, and ceramide, which were involved in glycerophospholipid and sphingolipid metabolism. The results of Western blotting analysis revealed that QFD could effectively alleviate heart failure through increasing the levels of lysophosphatidylcholine acyltransferase 1 (LPCAT1) and sphingomyelin synthase 1 (SMS1) and reducing the levels of acid sphingomyelinase (aSMase) and phospholipase A2 (PLA2) to regulate the metabolic disorders of glycerophospholipid and sphingolipid metabolism. All these results could be concluded that glycerophospholipid and sphingolipid metabolism were the two crucial target pathways for QFD against heart failure, which laid the theoretical groundwork for its clinical application.