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

Abstract

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.

Glucose Transporter 4 and Peroxisome Proliferator-Activated Receptor-Alpha Overexpression Association With Cardioprotective Effects of Myoinositol and Metformin Combination in Type 2 Diabetic Rat Model

“…Additionally, the accumulation of collagen fibers in the heart interstitium is another common finding of diabetic cardiomyopathy resulting in the inability of the heart to contract and relax efficiently [42]. In the current work, myocardial fibrosis was noticed in the diabetic group, consistent with other studies in different animal models of diabetes [43].…”

Mechanisms and Therapeutic Prospects of Diabetic Cardiomyopathy Through the Inflammatory Response

“…The anti-inflammatory effects of natural compounds are multifold, though varied among cell types. For instance, syringaresinol (SYR), a cereal extract, suppressed both Kelch-like ECH-associated protein 1 (KEAP1)/Nrf2 and TGFβ/Smad pathway in neonatal cardiomyocytes, resulting in reduced cardiac macrophage density and improved cardiac function ( Li et al, 2020 ). Interestingly, SYR can also downregulate NF-κB activation via p38 stimulation in macrophages in vitro , thereby reducing inflammation indirectly ( Bajpai et al, 2018 ).…”

Mechanism of Yangxinshi Intervention on Cardiac Fibrosis in Diabetic Cardiomyopathy Based on Network Pharmacology

“…Under the stimulation of high glucose environment, cardiac fibroblasts are activated into myofibroblasts, secreting a large amount of collagens, and extracellular matrix expands, thus promoting the occurrence of CF in DCM [20][21][22]. Hence, to avoid the development of diastolic heart failure [23,24] is to prevent and treat the pathological changes of CF in diabetic individuals.…”