Syringaresinol Protects against Type 1 Diabetic Cardiomyopathy by Alleviating Inflammation Responses, Cardiac Fibrosis, and Oxidative Stress

Scope Syringaresinol (SYR) is a phenolic compound, which could be found in various cereals and medicinal plants. It exerts both anti‐inflammatory and antioxidant pharmacological properties. However, little is known about the effect of SYR on modulating diabetic cardiomyopathy. The present study aimed to investigate the pharmacodynamic effect of SYR on diabetic cardiomyopathy and the underlying molecular mechanism. Methods and Results In STZ‐induced type 1 diabetic mice, orally administration with SYR in every other day for 8 weeks significantly improves cardiac dysfunction and preventes cardiac hypertrophy and fibrosis. The macrophage infiltration and oxidative stress biomarkers are also suppressed by SYR without affecting hyperglycemia and body weight. In neonatal cardiomyocytes, high glucose‐induced cell apoptosis and fibrosis are potently decreased by SYR, and the inflammatory response and oxidant stress are also alleviated by SYR incubation. Mechanistically, SYR may exert protective effects by restoring suppression of antioxidant kelch‐like ECH‐associated protein 1 (Keap1)/nuclear factor‐E2‐related factor 2 (Nrf2) system and abnormal activation of transforming growth factor‐β (TGF‐β)/mothers against decapentaplegic homolog (Smad) signaling pathway in vitro and in vivo. Conclusion The results indicated that SYR could be a potential therapeutic agent for the treatment of diabetic cardiomyopathy by inhibiting inflammation, fibrosis, and oxidative stress. The signaling pathway of Keap1/Nrf2 and TGF‐β/Smad could be used as therapeutic targets for diabetic complications. This study focus on the cardiac protecting role of SYR and its underlying mechanisms. SYR‐treated could attenuate oxidative stress, cardiac fibrosis, inflammation, and myocardial dysfunction in type 1 diabetic mice by activating the Keap1/Nrf2 system and suppressing the TGF‐β/Smad signaling pathway. These results suggested that SYR could be a potential therapeutic agent for the treatment of diabetic cardiomyopathy.