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Urinary Metabolomic Profiling Reveals the Effect of Shenfu Decoction on Chronic Heart Failure in Rats.

ABSTRACT: Shenfu decoction (SFD) can be used to treat patients with sign of Yangqi decline or Yang exhaustion related to chronic heart failure (CHF). We conducted a gas chromatography with time-of-flight mass spectrometer (GC/TOF-MS)-based metabolomic study to increase the understanding of CHF and assess the efficacies and mechanisms of SFD in treating CHF induced by coronary artery ligation in rats. Based on unsupervised principal component analysis, there was a clear separation between the CHF and sham surgery group, which revealed that CHF disturbed the metabolism of endogenous substances and significantly altered the urine metabolite fingerprints. After SFD treatment, the metabolomics profile found in CHF was significantly reversed, shifting much closer to normal controls and sham surgery group, indicating that SFD has therapeutic effects in CHF, which is in accordance with the hemodynamic assay results. Metabolomic pathway analysis demonstrated that several pathways including fatty acid biosynthesis, fatty acid elongation, steroid biosynthesis, galactose metabolism, and amino acid metabolism were significantly altered in CHF rats. Therefore, we may infer that SFD shows therapeutic efficacy in CHF by restoring these disturbed metabolic pathways, especially those related to energy metabolism. This study offers new methodologies for increasing the understanding of CHF and systematically characterizing the efficacies and mechanisms of SFD in treating CHF.

SUBMITTER: Yang D

PROVIDER: S-EPMC6332052 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature

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Urinary Metabolomic Profiling Reveals the Effect of Shenfu Decoction on Chronic Heart Failure in Rats.

Yang Dawei D Wang Xiaoxing X Wu Yaping Y Lu Bo B Yuan Aifeng A Leon Carlos C Guo Na N

Molecules (Basel, Switzerland) 20150630 7

Shenfu decoction (SFD) can be used to treat patients with sign of Yangqi decline or Yang exhaustion related to chronic heart failure (CHF). We conducted a gas chromatography with time-of-flight mass spectrometer (GC/TOF-MS)-based metabolomic study to increase the understanding of CHF and assess the efficacies and mechanisms of SFD in treating CHF induced by coronary artery ligation in rats. Based on unsupervised principal component analysis, there was a clear separation between the CHF and sham ...[more]

PMID: 26133758

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Project description:Traditional Chinese medicine is one of the complementary and alternative therapies to improve the prognosis of coronary heart disease (CHD). Taohong Siwu Decoction (THSWD), a classical traditional Chinese medication that promotes blood circulation, is clinically beneficial in CHD. However, the underlying mechanism of THSWD is still unclear. To comprehensively understand the material foundation of the "blood", it is significantly important to study the differential metabolites involved in the treatment of CHD with Chinese medicinal herb promoting blood circulation in TCM theory. Hence, this study investigated the metabolic profiles of the serum in CHD patients to determine the differential metabolites between the THSWD group and the placebo group. Eleven CHD patients were recruited and divided into two groups randomly and double-blindly. Serum samples were determined by performing non-targeted ultra-performance liquid chromatography with tandem mass spectrometry-based metabolomics. Pearson's correlation analysis was used to assess the association between identified metabolites and clinical serum indexes of CHD. Based on the result, a total of 513 metabolites were found in the serum of CHD patients, of which 27, involved in 29 metabolic pathways, were significantly different between the two groups. Among the differential metabolites, THSWD upregulated succinylcarnitine in fatty acid metabolism and 5'-methylthioadenosine in cysteine and methionine metabolism compared with the placebo group. However, THSWD downregulated pelargonic acid, involved in FA metabolism; succinate, involved in the tricarboxylic acid cycle; gluconic acid, gluconolactone, and d-glucose, involved in pentose phosphate pathway; glycerophosphocholine, involved in glycerophospholipid metabolism; 8,9-dihydroxyeicosatrienoic acid (8,9-DiHETrE), l-lysine, N-acetyl-l-aspartic acid, N-alpha-acetyl-l-asparagine, hippurate, indoxyl sulfate, and 3-ureidopropionate involved in amino acid metabolism compared with the placebo group. Moreover, succinylcarnitine, pelargonic acid, succinate, d-glucose, gluconic acid, l-lysine, N-alpha-acetyl-l-asparagine, 5'-methylthioadenosine, indoxyl sulfate, 8,9-DiHETrE, and 3-ureidopropionate were associated with total cholesterol or low-density lipoprotein. Succinylcarnitine, pelargonic acid, gluconolactone, N-acetyl-l-aspartic acid, N-alpha-acetyl-l-asparagine, hippurate, and 5'-methylthioadenosine were associated with activated partial thromboplastin time. Our findings indicated that glycerophosphocholine, 8,9-DiHETrE, 5'-methylthioadenosine, hippurate, indoxyl sulfate, and 3-ureidopropionate might constitute the partial material foundation of the "blood" in CHD patients treated with THSWD.

Project description:BACKGROUND:Lingguizhugan decoction (LGZG), an ancient Chinese herbal formula, has been used to treat cardiovascular diseases in eastern Asia. We investigated whether LGZG has protective activity and the mechanism underlying its effect in an animal model of heart failure (HF). METHODS:A rat model of HF was established by administering eight intraperitoneal injections of doxorubicin (DOX) (cumulative dose of 16?mg/kg) over a 4-week period. Subsequently, LGZG at 5, 10, and 15?mL/kg/d was administered to the rats intragastrically once daily for 4?weeks. The body weight, heart weight index (HWI), heart weight/tibia length ratio (HW/TL), and serum BNP level were investigated to assess the effect of LGZG on HF. Echocardiography was performed to investigate cardiac function, and H&E staining to visualize myocardial morphology. Myocardial ultrastructure and T-tubule-sarcoplasmic reticulum (TT-SR) junctions were observed by transmission electron microscopy. The JP-2 protein level was determined by Western blotting. The mRNA level of CACNA1S and RyR2 and the microRNA-24 (miR-24) level were assayed by quantitative RT-PCR. RESULTS:Four weeks after DOX treatment, rats developed cardiac damage and exhibited a significantly increased BNP level compared with the control rats (169.6?±?29.6?pg/mL versus 80.1?±?9.8?pg/mL, P?<?0.001). Conversely, LGZG, especially at the highest dose, markedly reduced the BNP level (93.8?±?17.9?pg/mL, P?<?0.001). Rats treated with DOX developed cardiac dysfunction, characterized by a strong decrease in left ventricular ejection fraction compared with the control (58.5?±?8.7% versus 88.7?±?4.0%; P?<?0.001). Digoxin and LGZG improved cardiac dysfunction (79.6?±?6.1%, 69.2?±?2.5%, respectively) and preserved the left ventricular ejection fraction (77.9?±?5.1, and 80.5?±?4.9, respectively, P?<?0.01). LGZG also improved the LVEDD, LVESD, and FS and eliminated ventricular hypertrophy, as indicated by decreased HWI and HW/TL ratio. LGZG attenuated morphological abnormalities and mitochondrial damage in the myocardium. In addition, a high dose of LGZG significantly downregulated the expression of miR-24 compared with that in DOX-treated rats (fold change 1.4 versus 3.4, P?<?0.001), but upregulated the expression of JP-2 and antagonized DOX-induced T-tubule TT-SR microstructural remodeling. These activities improved periodic Ca2+ transients and cell contraction, which may underly the beneficial effect of LGZG on HF. CONCLUSIONS:LGZG exerted beneficial effects on DOX-induced HF in rats, which were mediated in part by improved TT-SR microstructural remodeling.

Dataset Information

Urinary Metabolomic Profiling Reveals the Effect of Shenfu Decoction on Chronic Heart Failure in Rats.

Publications

Urinary Metabolomic Profiling Reveals the Effect of Shenfu Decoction on Chronic Heart Failure in Rats.

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