Resveratrol Inhibits High Glucose-Induced H9c2 Cardiomyocyte Hypertrophy and Damage via RAGE-Dependent Inhibition of the NF-κB and TGF-β1/Smad3 Pathways.

TRANSFORMING growth factors-beta; REVERSE transcriptase polymerase chain reaction; CYTOKINES; HYPERGLYCEMIA; MYOCARDIUM; HEART cells; POLYPHENOLS; CARDIAC hypertrophy; ANIMAL experimentation; WESTERN immunoblotting; CELL receptors; APOPTOSIS; FIBROSIS; RESVERATROL; CELLULAR signal transduction; RATS; DNA-binding proteins; MOLECULAR structure; POLYMERASE chain reaction; EXTRACELLULAR space; CARRIER proteins; CARDIOTONIC agents; DISEASE complications

Hyperglycaemia is associated with the development of cardiac vascular disease. Resveratrol (RES) is a naturally occurring polyphenolic compound that possesses many biological properties, including anti-inflammatory properties and antioxidation functions. Our study aimed to explore the RES's protective roles on high glucose (HG)-induced H9c2 cells and the underlying mechanisms. Small-molecule inhibitors, western blotting (WB), as well as reverse-transcription PCR (RT-PCR) were employed to investigate the mechanisms underlying HG-induced damage in H9c2 cells. RES (40 μg/mL) treatment significantly alleviated HG-induced cardiac hypertrophy and cardiac dysfunction. RES abated the HG‐induced increase in the levels of extracellular matrix (ECM) components and inflammatory cytokines, reducing ECM accumulation and inflammatory responses. Additionally, RES administration prevented HG‐induced mitochondrion‐mediated cardiac apoptosis of myocardial cells. In terms of mechanisms, we demonstrated that RES ameliorated the HG‐induced overexpression of receptor for advanced glycation endproducts (RAGE) and downregulation of NF-κB signalling. Moreover, RES inhibited HG‐induced cardiac fibrosis by inhibiting transforming growth factor beta 1 (TGF‐β1)/Smad3‐mediated ECM synthesis in cultured H9c2 cardiomyocytes. Further studies revealed that the effects of RES against HG‐induced upregulation of NF-κB and TGF‐β1/Smad3 pathways were similar to those of FPS-ZM1, a RAGE inhibitor. Collectively, the results implied that RES might help alleviate HG‐induced cardiotoxicity via RAGE‐dependent downregulation of the NF-κB and TGF‐β/Smad3 pathways. This study provided evidence that RES can be developed as a promising cardioprotective drug. [ABSTRACT FROM AUTHOR]

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