Cinnamaldehyde attenuates diabetic cardiomyopathy by ameliorating energy metabolism disturbance and activating autophagy

Diabetic Cardiomyopathy (DCM) is a diabetes mellitus-induced pathophysiological condition that can lead to heart failure. Cinnamaldehyde (CA), a bioactive phytochemical derived from the bark of Cinnamon , exhibits cardioprotective properties against heart injury in metabolic syndrome. This study aims to explore the role of CA on DCM and its cardioprotective mechanisms. Diabetic rats were established by injection of streptozotocin (STZ, 60∼85 mg/kg). Subsequently, CA (50 mg/kg) was administered via gavage daily for 28-day duration. Following this treatment, abnormalities levels of fasting blood glucose (FBG), triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and LDL-C to HDL-C ratio were ameliorated. Additionally, CA inhibited cardiac histopathological alterations and hypertrophy, reduced brain natriuretic peptide (BNP) level, shortened S-T and P-R intervals on electrocardiogram, decreased tissue malondialdehyde content, and enhanced myocardial energy metabolism, including Creatine (Cr), adenosine triphosphate (ATP), adenosine monophosphate (AMP) and total adenine nucleotides (TAN). Furthermore, CA improved oxidative stress, improved myocardial Ca 2+ -Mg 2+ -ATPase activity and downregulated the mRNA expression of AMP protein activation kinase α2 (AMPK-α2), receptor γ coactivator-1 alpha (PGC-1α) and peroxisome proliferator-activated receptor α (PPARα), while also ameliorating protein expressions, including ratio of phosphorylated mammalian target of rapamycin to mechanistic target of rapamycin (p-mTOR/mTOR), level of SQSTM1/p62, and ratio of microtubule-associated protein 1 light chain 3 beta to microtubule-associated protein 1 light chain 3 alpha (LC3Ⅱ/ LC3Ⅰ). In conclusion, these findings indicate that CA can alleviate DCM by modulating AMPK-α2/PPAR-α/PGC-1α signaling pathway to restore energy metabolism and activating autophagy through mTOR signaling pathway.