Si-Miao-Yong-An decoction preserves cardiac function and regulates GLC/AMPK/NF-κB and GLC/PPARα/PGC-1α pathways in diabetic mice

Abstract

Background: Diabetic cardiomyopathy (DCM) is a main cause of heart failure and death in diabetic patients. However, countermeasures to limit the development of this disease remain insufficient. Si-Miao-Yong-An decoction (SMYA), a Chinese herbal prescription, exhibits both lipid-lowering and cardiovascular preserving effects, and may have an effect on DCM management.

Purpose: The current study is aimed to investigate the effects of SMYA on the cardiac function in diabetic mice and the underlying mechanisms involved.

Methods: Streptozotocin-induced diabetic mice were fed intragastrically with SMYA every day for 15 weeks. Cardiac function was assessed by echocardiograph. Histopathological alterations in the heart were determined by hematoxylin/eosin, wheat germ agglutinin, Masson's trichrome, Terminal dUTP nick end-labeling, Oil red O staining, and transmission electron microscopy. The potential involvements of GLC/AMPK/NF-κB and GLC/PPARα/PGC-1α signaling pathways were investigated by western blot and/or immunohistochemical staining.

Results: Treatment of diabetic mice with SMYA improved insulin sensitivity, and attenuated the increases of water consumption, food intake, blood glucose, and serum GLC. Furthermore, SMYA ameliorated cardiac systolic and diastolic functions, suppressed the myocardial hypertrophy, fibrosis, apoptosis, inflammation, and lipid accumulation as well as preserved the myofilaments arrangement and mitochondrial integrity. Finally, SMYA downregulated the expressions of GCGR, PGC-1α, PPARα and the phosphorylation of NF-κB, as well as upregulated the phosphorylation of AMPK in the hearts of diabetic mice.

Conclusions: SMYA may ameliorate glucolipid metabolism and cardiac function through the regulation of GLC/AMPK/NF-κB and GLC/PPARα/PGC-1α signaling pathways in diabetic mice, suggesting that this prescription could provide a new source of drug candidates to protect against DCM.

Keywords: AMPK/NF-κB; Diabetic cardiomyopathy; Glucagon; PPARα/PGC-1α; Si-Miao-Yong-An decoction.