Compound danshen dripping pills modulate the perturbed energy metabolism in a rat model of acute myocardial ischemia

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Abstract

The continuous administration of compound danshen dripping pills (CDDP) showed good efficacy in relieving myocardial ischemia clinically. To probe the underlying mechanism, metabolic features were evaluated in a rat model of acute myocardial ischemia induced by isoproterenol (ISO) and administrated with CDDP using a metabolomics platform. Our data revealed that the ISO-induced animal model showed obvious myocardial injury, decreased energy production, and a marked change in metabolomic patterns in plasma and heart tissue. CDDP pretreatment increased energy production, ameliorated biochemical indices, modulated the changes and metabolomic pattern induced by ISO, especially in heart tissue. For the first time, we found that ISO induced myocardial ischemia was accomplished with a reduced fatty acids metabolism and an elevated glycolysis for energy supply upon the ischemic stress; while CDDP pretreatment prevented the tendency induced by ISO and enhanced a metabolic shift towards fatty acids metabolism that conventionally dominates energy supply to cardiac muscle cells. These data suggested that the underlying mechanism of CDDP involved regulating the dominant energy production mode and enhancing a metabolic shift toward fatty acids metabolism in ischemic heart. It was further indicated that CDDP had the potential to prevent myocardial ischemia in clinic.

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Myocardial fatty acid metabolism in health and disease.

Gary D. Lopaschuk, John Ussher, Clifford D L Folmes … (2010)

There is a constant high demand for energy to sustain the continuous contractile activity of the heart, which is met primarily by the beta-oxidation of long-chain fatty acids. The control of fatty acid beta-oxidation is complex and is aimed at ensuring that the supply and oxidation of the fatty acids is sufficient to meet the energy demands of the heart. The metabolism of fatty acids via beta-oxidation is not regulated in isolation; rather, it occurs in response to alterations in contractile work, the presence of competing substrates (i.e., glucose, lactate, ketones, amino acids), changes in hormonal milieu, and limitations in oxygen supply. Alterations in fatty acid metabolism can contribute to cardiac pathology. For instance, the excessive uptake and beta-oxidation of fatty acids in obesity and diabetes can compromise cardiac function. Furthermore, alterations in fatty acid beta-oxidation both during and after ischemia and in the failing heart can also contribute to cardiac pathology. This paper reviews the regulation of myocardial fatty acid beta-oxidation and how alterations in fatty acid beta-oxidation can contribute to heart disease. The implications of inhibiting fatty acid beta-oxidation as a potential novel therapeutic approach for the treatment of various forms of heart disease are also discussed.

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Stable angina pectoris with no obstructive coronary artery disease is associated with increased risks of major adverse cardiovascular events.

Lasse Jespersen, Anders Hvelplund, Steen Abildstrøm … (2012)

Patients with chest pain and no obstructive coronary artery disease (CAD) are considered at low risk for cardiovascular events but evidence supporting this is scarce. We investigated the prognostic implications of stable angina pectoris in relation to the presence and degree of CAD with no obstructive CAD in focus. We identified 11 223 patients referred for coronary angiography (CAG) in 1998-2009 with stable angina pectoris as indication and 5705 participants from the Copenhagen City Heart Study for comparison. Main outcome measures were major adverse cardiovascular events (MACE), defined as cardiovascular death, myocardial infarction, stroke or heart failure, and all-cause mortality. Significantly more women (65%) than men (32%) had no obstructive CAD (P< 0.001). In Cox's models adjusted for age, body mass index, diabetes, smoking, and use of lipid-lowering or antihypertensive medication, hazard ratios (HRs) associated with no obstructive CAD were similar in men and women. In the pooled analysis, the risk of MACE increased with increasing degrees of CAD with multivariable-adjusted HRs of 1.52 (95% confidence interval, 1.27-1.83) for patients with normal coronary arteries and 1.85 (1.51-2.28) for patients with diffuse non-obstructive CAD compared with the reference population. For all-cause mortality, normal coronary arteries and diffuse non-obstructive CAD were associated with HRs of 1.29 (1.07-1.56) and 1.52 (1.24-1.88), respectively. Patients with stable angina and normal coronary arteries or diffuse non-obstructive CAD have elevated risks of MACE and all-cause mortality compared with a reference population without ischaemic heart disease.

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Ketone bodies: a review of physiology, pathophysiology and application of monitoring to diabetes.

L Laffel (2000)

Ketone bodies are produced by the liver and used peripherally as an energy source when glucose is not readily available. The two main ketone bodies are acetoacetate (AcAc) and 3-beta-hydroxybutyrate (3HB), while acetone is the third, and least abundant, ketone body. Ketones are always present in the blood and their levels increase during fasting and prolonged exercise. They are also found in the blood of neonates and pregnant women. Diabetes is the most common pathological cause of elevated blood ketones. In diabetic ketoacidosis (DKA), high levels of ketones are produced in response to low insulin levels and high levels of counterregulatory hormones. In acute DKA, the ketone body ratio (3HB:AcAc) rises from normal (1:1) to as high as 10:1. In response to insulin therapy, 3HB levels commonly decrease long before AcAc levels. The frequently employed nitroprusside test only detects AcAc in blood and urine. This test is inconvenient, does not assess the best indicator of ketone body levels (3HB), provides only a semiquantitative assessment of ketone levels and is associated with false-positive results. Recently, inexpensive quantitative tests of 3HB levels have become available for use with small blood samples (5-25 microl). These tests offer new options for monitoring and treating diabetes and other states characterized by the abnormal metabolism of ketone bodies. Copyright 1999 John Wiley & Sons, Ltd.

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Author and article information

Journal

Journal ID (nlm-ta): Sci Rep

Journal ID (iso-abbrev): Sci Rep

Title: Scientific Reports

Publisher: Nature Publishing Group

ISSN (Electronic): 2045-2322

Publication date (Electronic): 01 December 2016

Publication date Collection: 2016

Volume: 6

Electronic Location Identifier: 37919

Affiliations

[1 ]Key Laboratory of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, Key laboratory of drug design and optimization, China Pharmaceutical University , No. 24 TongjiaLane, Nanjing, 210009, China

[2 ]State Key Laboratory of Core Technology in Innovative Chinese Medicine, Tasly R&D Institute, Tianjin Tasly Group Co., Ltd. , No. 2 Pujihe East Road, Tianjin, 300410, China

[3 ]Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University , No. 300 Guangzhou Avenue, Nanjing, 210029, China

[4 ]Key Lab of Chinese Medicine, Nanjing University of Chinese Medicine , No. 282 Hanzhong Road, Nanjing, 210029, China

[5 ]School of Pharmaceutical Science and Technology, Tianjin University , No. 92 Weijin Road, Tianjin, 300072, China

Author notes

[a ] jiyea@ 123456cpu.edu.cn

[b ] guangjiwang@ 123456hotmail.com

[*]

These authors contributed equally to this work.

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Publisher Item ID: srep37919

DOI: 10.1038/srep37919

PMC ID: 5131350

PubMed ID: 27905409

SO-VID: aae16bfa-bd1c-4fb7-9679-3b381ae8f336

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Compound danshen dripping pills modulate the perturbed energy metabolism in a rat model of acute myocardial ischemia

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Cancer Metabolism

Most cited references 33

Myocardial fatty acid metabolism in health and disease.

Stable angina pectoris with no obstructive coronary artery disease is associated with increased risks of major adverse cardiovascular events.

Ketone bodies: a review of physiology, pathophysiology and application of monitoring to diabetes.

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