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

Background: 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 improved cardiac dysfunction and prevented cardiac hypertrophy and fibrosis. The macrophage infiltration and oxidative stress biomarkers were also suppressed by SYR distinctly without affecting hyperglycemia and body weight. In neonatal cardiomyocytes, high glucose-induced cell apoptosis and fibrosis were potently decreased by SYR, and the inflammatory response and oxidant stress were also alleviated by SYR incubation. Mechanistically, SYR may exert its protective effects by restoring suppression of antioxidant Keap1/Nrf2 system and abnormal activation of TGF-β/Smad signaling pathway both 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 article is protected by copyright. All rights reserved.

Keywords: diabetic cardiomyopathy; fibrosis; inflammation; oxidative stress; syringaresinol.