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Shengmai San Alleviates Diabetic Cardiomyopathy Through Improvement of Mitochondrial Lipid Metabolic Disorder.
Shengmai San Alleviates Diabetic Cardiomyopathy Through Improvement of Mitochondrial Lipid Metabolic Disorder.
- Source :
-
Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology [Cell Physiol Biochem] 2018; Vol. 50 (5), pp. 1726-1739. Date of Electronic Publication: 2018 Nov 01. - Publication Year :
- 2018
-
Abstract
- Background/aims: Shengmai San (SMS), prepared from Panax ginseng, Ophiopogon japonicus, and Schisandra chinensisin, has been widely used to treat ischemic disease. In this study, we investigated whether SMS may exert a beneficial effect in diabetic cardiomyopathy through improvement of mitochondrial lipid metabolism.<br />Methods: A leptin receptor-deficient db/db mouse model was utilized, and lean age-matched C57BLKS mice served as non-diabetic controls. Glucose and lipid profiles, myocardial structure, dimension, and function, and heart weight to tibial length ratio were determined. Myocardial ultrastructural morphology was observed with transmission electron microscopy. Protein expression and activity of oxidative phosphorylation (OXPHOS) complex were assessed using western blotting and microplate assay kits. We also observed cellular viability, mitochondrial membrane potential, OXPHOS complex activity, and cellular ATP level in palmitic acid-stimulated H9C2 cardiomyocytes. Changes in the sirtuin (SIRT1)/AMP-activated protein kinase (AMPK)/peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) pathway and mitochondrial uncoupling signaling were assessed using western blotting and quantitative real-time PCR.<br />Results: Leptin receptor-deficient db/db mice exhibit obesity, hyperglycemia, and hyperlipidemia, accompanied by distinct myocardial hypertrophy and diastolic dysfunction. SMS at a dose of 3 g/kg body weight contributed to a recovery of diabetes-induced myocardial hypertrophy and diastolic dysfunction. SMS administration led to an effective restoration of mitochondrial structure and function both in vivo and in vitro. Furthermore, SMS markedly enhanced SIRT1 and p-AMPKα protein levels and decreased the expression of acetylated-PGC-1α and uncoupling protein 2 protein. SMS also restored the depletion of NRF1 and TFAM levels in diabetic hearts and H9C2 cardiomyocytes.<br />Conclusion: The results indicate that SMS may alleviate diabetes-induced myocardial hypertrophy and diastolic dysfunction by improving mitochondrial lipid metabolism.<br /> (© 2018 The Author(s). Published by S. Karger AG, Basel.)
- Subjects :
- AMP-Activated Protein Kinases metabolism
Animals
Diabetes Mellitus, Type 2 complications
Diabetes Mellitus, Type 2 pathology
Diabetes Mellitus, Type 2 veterinary
Diabetic Cardiomyopathies drug therapy
Diabetic Cardiomyopathies etiology
Diabetic Cardiomyopathies pathology
Drug Combinations
Drugs, Chinese Herbal therapeutic use
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Mitochondria metabolism
Myocardium metabolism
Myocardium pathology
Myocytes, Cardiac cytology
Myocytes, Cardiac drug effects
Myocytes, Cardiac metabolism
Nuclear Respiratory Factor 1 metabolism
Oxidative Phosphorylation drug effects
Palmitic Acid pharmacology
Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha metabolism
Receptors, Leptin deficiency
Receptors, Leptin genetics
Signal Transduction drug effects
Sirtuin 1 metabolism
Uncoupling Protein 2 metabolism
Drugs, Chinese Herbal pharmacology
Mitochondria drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1421-9778
- Volume :
- 50
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 30384366
- Full Text :
- https://doi.org/10.1159/000494791