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Si-Miao-Yong-An decoction preserves cardiac function and regulates GLC/AMPK/NF-κB and GLC/PPARα/PGC-1α pathways in
Lin Li1, Xiangyang Chen2, Congping Su1
1School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, 100029, China.
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.
Insights
Si-Miao-Yong-An decoction (SMYA) improved cardiac function in diabetic mice by regulating glucolipid metabolism and key signaling pathways. This traditional Chinese medicine may offer new therapeutic strategies for diabetic cardiomyopathy (DCM).
Area of Science:
- Cardiovascular Research
- Metabolic Diseases
- Pharmacology
Background:
- Diabetic cardiomyopathy (DCM) is a significant complication of diabetes, leading to heart failure and increased mortality.
- Current treatments for DCM are insufficient, highlighting the need for novel therapeutic approaches.
- Si-Miao-Yong-An decoction (SMYA), a Chinese herbal formula, has demonstrated lipid-lowering and cardioprotective properties, suggesting potential in DCM management.
Purpose of the Study:
- To investigate the therapeutic effects of SMYA on cardiac function in a mouse model of diabetes.
- To elucidate the underlying molecular mechanisms by which SMYA influences diabetic cardiomyopathy.
Main Methods:
- Diabetic mice were induced using streptozotocin and treated with SMYA for 15 weeks.
- Cardiac function was evaluated using echocardiography.
- Histopathological analyses included H&E, WGA, Masson's trichrome, TUNEL, Oil red O, and transmission electron microscopy.
- Western blot and immunohistochemistry were employed to assess signaling pathway activation (GLC/AMPK/NF-κB and GLC/PPARα/PGC-1α).
Main Results:
- SMYA treatment improved insulin sensitivity and attenuated hyperglycemia, polydipsia, and polyphagia in diabetic mice.
- Cardiac function was significantly improved, with reduced myocardial hypertrophy, fibrosis, apoptosis, inflammation, and lipid accumulation.
- SMYA preserved cardiac myofilament structure and mitochondrial integrity.
- Key molecular changes included downregulation of GCGR, PGC-1α, PPARα, and p-NF-κB, and upregulation of p-AMPK.
Conclusions:
- SMYA ameliorates glucolipid metabolism and cardiac dysfunction in diabetic mice.
- The protective effects are mediated through the modulation of GLC/AMPK/NF-κB and GLC/PPARα/PGC-1α signaling pathways.
- SMYA shows promise as a potential therapeutic agent for preventing and treating diabetic cardiomyopathy.
