Metabonomic Strategy to the Evaluation of Chinese Medicine Compound Danshen Dripping Pills Interfering Myocardial Ischemia in Rats

Abstract

Coronary heart disease (CHD) is one of the highest mortality diseases in the world. Traditional Chinese medicine compound Danshen dripping pills (CDDPs) have currently made a great achievement in treating CHD. However, the therapeutic mechanism of CDDP is often poorly interpreted. In this study, a GC-MS-based metabonomic study was conducted to assess the holistic efficacy of CDDP for myocardial infarction in male Sprague-Dawley rats, which were divided into the control group, the sham group, the model group, the control + CDDP group, and the model + CDDP, with CDDP at a dose of 107 mg/kg·d (equal to 1.8 mL/kg·d). The metabonomic findings demonstrated great differences of metabolic pattern among sham, model, and the model + CDDP in the orthogonal partial least squares discriminant analysis (OPLS-DA) models, which coordinated well with the assessment of plasma biochemistry and histopathological assay. Differentially expressed metabolites suggested that energy metabolism, glycolysis, and lipid metabolism might be disrupted by myocardial infarction. Both the potential metabolic biomarkers and the biochemical histopathological indices were regulated effectively by CDDP.

Metabolic Characterization of Myocardial Infarction Using GC-MS-Based Tissue Metabolomics

“…Most ischemia-related differential metabolites are involved in the metabolic processes related to myocardial energy metabolism, including the TCA cycle, glycolysis, fatty acid beta oxidation, and ATP production. The current tissue metabolomics confirms several previous results in clinical or animal MI studies using serum metabolomics, 8,9,14) that most fatty acids and TCA intermediate metabolites are significantly decreased, and lactate is increased post MI. The heart has an abundant source of fuels, which mainly include fatty acids, glucose, and keto-bodies.…”

“…Coronary artery ligation (CAL) rat models are widely used to study related pathophysiological alterations of MI, or to explore the effect of drug treatment. 8,9) However, CAL animal studies are easily influenced by the operation itself, even if a control group has been established. Thus, we designed a self-control study here.…”

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“…14 In the present study, CDDP had several protective effects on ischemic myocardium and improved cardiac function by decreasing apoptosis, oxidative stress, and inflammation, consistent with previous reports. [8][9][10] The survival of implanted human umbilical cord blood mononuclear cells was improved in rabbits treated with CDDP. In addition, CDDP alone had an inhibitory effect on inflammation and oxidative stress in the infarcted heart, and improvement in cardiac function was similar with CDDP alone or human umbilical cord blood mononuclear cells alone.…”

“…The mechanism for the protective effects of CDDP is unknown and may include (1) inhibition of Intercellular Adhesion Molecule 1 (ICAM-1) and granulocyte adherence factor CDIIB/CD18 expression, with associated inhibition of leukocytic infiltration; (2) decreased release of proinflammatory factors (tumor necrosis factor α and interleukin 6) by inhibition of monocyte and macrophage degranulation; (3) decreased production of peroxide in ischemic tissues; and (4) dilation of coronary arteries and improved microcirculation. [8][9][10][14][15][16] There are several limitations of the present study. It is unknown whether or not the grafted mononuclear cells in the myocardium differentiated into myocardial cells.…”

“…[8][9][10] We hypothesized that treatment with CDDP may improve the cardiac microenvironment created by acute myocardial infarction and may improve the survival and therapeutic efficacy of implanted human umbilical cord blood mononuclear cells in vivo.…”