Cardioprotective effects of Cinnamomum migao water extract against acute myocardial infarction: insights from integrated untargeted and spatial metabolomics into glycerophospholipid metabolism and SRC/PI3K/AKT signaling

Abstract Background Acute myocardial infarction (AMI) induces profound metabolic disturbances that aggravate cardiomyocyte injury and impair cardiac function. Modulating these disturbances may provide novel strategies for myocardial protection. Cinnamomum migao , a traditional ethnic medicinal herb for cardiovascular disorders, is historically administered as a decoction. While previous studies have focused on its volatile oil fraction, the cardioprotective effects and mechanisms of its water extract (CMW), consistent with traditional use, remain insufficiently characterized. Purpose This study aimed to systematically evaluate the cardioprotective effects of CMW against AMI and elucidate the underlying mechanisms associated with its metabolic regulation. Methods A mouse AMI model was established by left anterior descending coronary artery ligation. Cardioprotective effects of CMW were assessed via electrocardiography, infarct size, serum biomarkers, and histopathology. LC-HRMS-based untargeted metabolomics combined with AFADESI mass spectrometry imaging was employed to characterize myocardial metabolic alterations and spatial distribution of key metabolites. Serum pharmacochemistry, target prediction, and molecular validation were further applied to explore potential mechanisms. Results CMW markedly attenuated AMI-induced myocardial injury, evidenced by reduced infarct size, decreased serum biomarkers, and improved histopathology. Metabolomics revealed that CMW reversed AMI-associated disturbances, with glycerophospholipid metabolism identified as a key pathway. AFADESI imaging confirmed partial normalization of phosphocholine, lysophosphatidylcholine (22:5), and glycerophosphocholine distribution. Serum pharmacochemistry identified absorbed constituents including chlorogenic acid, neochlorogenic acid, naringin, afzelin, quercitrin, and norboldine. Molecular validation demonstrated that CMW activated SRC/PI3K/AKT signaling and restored Bcl-2/Bax balance in AMI myocardium. Conclusion CMW exerts cardioprotective effects against AMI by ameliorating glycerophospholipid metabolic disturbances and activating SRC/PI3K/AKT-associated signaling. Integration of untargeted and spatial metabolomics provides complementary evidence for its metabolic regulatory actions, offering a modern pharmacological interpretation of the traditional decoction use of Cinnamomum migao .