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Plasma metabonomics study on Chinese medicine syndrome evolution of heart failure rats caused by LAD ligation.

ABSTRACT: BACKGROUND: Chinese medicine syndromes (Zheng) in many disease models are not clearly characterized or validated, and the concepts of Chinese medicine syndromes are confounding and controversial. Metabonomics has been applied to the evaluation and classification of the Chinese medicine syndromes both in clinical and nonclinical studies. In this study, we aim to investigate the evolution of the Chinese medicine syndrome in myocardial infarction induced heart failure and to confirm the feasibility of the Zheng classification by plasma metabonomics in a syndrome and disease combination animal model. METHODS: The heart failure (HF) model was induced by ligation of the left anterior descending coronary artery (LAD) in Sprague-Dawley rats. The rats were divided into the following two groups: the HF model group (LAD ligation) and the sham operated group. GC-MS was used with pattern recognition technology and principal component analysis (PCA) to analyze the plasma samples at 4, 21 and 45 day after operation. RESULTS: It was determined that the period from 7 to 28 days was the stable time window of ischemic heart failure with qi deficiency and blood stasis syndrome (QDBS), and the qi deficiency syndrome occurred at 1 to 4 days and 45 to 60 days after operation. The results exhibited 5 plasma metabolite changes in the same trend at 4 and 21 day after the LAD operation, 7 at 21 and 45 day, and 2 at 4 and 45 day. No metabolite showed the same change at all of the 3 time points. At day 21 (the QDBS syndrome time point) after operation, 4 plasma metabolites showed the same trends with the results of our previous study on patients with the blood stasis syndrome. CONCLUSIONS: The syndrome diagnosis is reliable in the HF rat model in this study. Plasma metabolites can provide a basis for the evaluation of Chinese medicine syndrome animal models.

SUBMITTER: Qiu Q

PROVIDER: S-EPMC4227006 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Plasma metabonomics study on Chinese medicine syndrome evolution of heart failure rats caused by LAD ligation.

Qiu Qi Q Li Chun C Wang Yong Y Xiao Cheng C Li Yu Y Lin Yang Y Wang Wei W

BMC complementary and alternative medicine 20140709

<h4>Background</h4>Chinese medicine syndromes (Zheng) in many disease models are not clearly characterized or validated, and the concepts of Chinese medicine syndromes are confounding and controversial. Metabonomics has been applied to the evaluation and classification of the Chinese medicine syndromes both in clinical and nonclinical studies. In this study, we aim to investigate the evolution of the Chinese medicine syndrome in myocardial infarction induced heart failure and to confirm the feas ...[more]

PMID: 25012233

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Project description:BackgroundTraditional Chinese medicine (TCM) has gained widespread application in treating chronic heart failure (CHF) secondary to coronary heart disease (CHD). However, the sound clinical evidence is still lacking. Corresponding clinical trials vary considerably in the outcome measures assessing the efficacy of TCM, some that showed the improvement of clinical symptoms are not universally acknowledged. Rational outcome measures are the key to evaluate efficacy and safety of each treatment and significant elements of a convincing clinical trial. We aimed to summarize and analyze outcome measures in randomized controlled trials (RCTs) of TCM in treating CHF caused by CHD, subsequently identify the present problems and try to put forward solutions.MethodsWe systematically searched databases including Embase, PubMed, Cochrane Library, CBM, CNKI, VIP and Wanfang from inception to October 8, 2018, to identify eligible RCTs using TCM interventions for treating CHF patients caused by CHD. Cochrane Database of Systematic Reviews (CDSR) was searched to include Cochrane systematic reviews (CSRs) of CHF. Two authors independently assessed the risk of bias of the included RCTs according to the Cochrane Handbook. Outcome measures of each trial were extracted and analyzed those compared with the CSRs. We also evaluated the reporting quality of the outcome measures.ResultsA total of 31 RCTs were included and the methodology quality of the studies was generally low. Outcome measures in these RCTs were mortality, rehospitalization, efficacy of cardiac function, left ventricular ejection fraction (LVEF), 6 min' walk distance (6MWD) and Brain natriuretic peptide (BNP), of which mortality and rehospitalization are clinical end points while the others are surrogate outcomes. The reporting rate of mortality and rehospitalization was 12.90% (4/31), the other included studies reported surrogate outcomes. As safety measure, 54.84% of the studies reported adverse drug reactions. Two trials were evaluated as high in reporting quality of outcomes and that of the other 29 studies was poor due to lack of necessary information for reporting.ConclusionsThe present RCTs of TCM in treating CHF secondary to CHD did not concentrate on the clinical end points of heart failure, which were generally small in size and short in duration. Moreover, these trials lacked adequate safety evaluation, had low quality in reporting outcomes and certain risk of bias in methodology. For objective assessment of the efficacy and safety of TCM in treating CHF secondary to CHD, future research should be rigorous designed, set end points as primary outcome measures and pay more attention to safety evaluation throughout the trial.

Project description:BackgroundPoge heart-saving decoction (PHSD) has been used as a medicine treating heart failure in China for many years. The study aimed to explore the effect of PHSD on cardiac function in heart failure conditions and its underlying mechanism.MethodsAdriamycin was used to induce the model of heart failure (HF) in rats. Sixty rats were randomly divided into six groups: blank control group, sham group, 9.33 g/kg group (low-PHSD, test group), 13.995 g/kg group (moderate-PHSD, test group), 18.66 g/kg group (high-PHSD, test group), and fosinopril group (4.67 mg/kg, comparison test group). Cardiac ultrasound was used to evaluate the cardiac function of the rats, and radioimmunoassay was used to measure aldosterone (ALD) and angiotensin II (AngII) levels in the serum.ResultsCompared with the blank control group, the left ventricular end-diastolic dimension (LVEDd) and left ventricular end-systolic dimension (LVEDs) in the sham group were increased (1.04 ± 0.12 vs. 0.67 ± 0.13 cm; 0.75 ± 0.13 vs. 0.28 ± 0.10 cm; P < 0.05), and the left ventricular ejection fraction was decreased (36.65 ± 5.74 vs. 76.09 ± 4.23%; P < 0.05). The ejection fraction of HF rats was increased in 9.33 g/kg group, 13.995 g/kg group, and 18.66 g/kg group compared with those of the sham group (57.13 ± 1.63, 58.43 ± 1.98, and 59.21 ± 1.37 vs. 36.65 ± 5.74%; P < 0.05). PHSD also improved cardiac function by reducing the LVEDd and LVEDs (0.88 ± 0.11, 0.75 ± 0.13, and 0.72 ± 0.18 vs. 1.04 ± 0.12 cm; 0.62 ± 0.10, 0.63 ± 0.17, and 0.45 ± 0.11 vs. 0.75 ± 0.13 cm; P < 0.05). The levels of ALD and AngII in the serum of rats in the sham group were significantly higher than those in the blank control group (371.58 ± 39.25 vs. 237.12 ± 17.35 μg/L; 232.18 ± 16.33 vs. 159.44 ± 18.42 pg/L; P < 0.05). The ALD and AngII of the rats in all of the three PHSD groups and the fosinopril group were decreased (276.81 ± 25.63, 277.18 ± 21.35, 268.19 ± 19.28, and 271.47 ± 28.96 vs. 371.58 ± 39.25 μg/L; 169.41 ± 27.53, 168.81 ± 19.78, 164.23 ± 21.34, and 174.27 ± 22.84 vs. 232.18 ± 16.33 pg/L; P < 0.05). The histopathological changes of the myocardium in the sham group showed the disorganized fiber, shaded staining, fracture, and zonation. The fracture of the myocardium was relieved in all groups except the sham group and the blank control group.ConclusionTherefore, PHSD could shorten LVEDd and LVEDs of rats and reverse ventricular remodeling. The mechanism might be related to the inhibition of the activation level of renin-angiotensin-aldosterone system (especially ALD and AngII) and decreasing the postload of the heart.

Project description:Chronic heart failure (CHF) is a major public health problem in huge population worldwide. The detailed understanding of CHF mechanism is still limited. Zheng (syndrome) is the criterion of diagnosis and therapeutic in Traditional Chinese Medicine (TCM). Syndrome prediction may be a better approach for understanding of CHF mechanism basis and its treatment. The authors studied disturbed metabolic biomarkers to construct a predicting mode to assess the diagnostic value of different syndrome of CHF and explore the Chinese herbal medicine (CHM) efficacy on CHF patients. A cohort of 110 patients from 11 independent centers was studied and all patients were divided into 3 groups according to TCM syndrome differentiation: group of Qi deficiency syndrome, group of Qi deficiency and Blood stasis syndrome, and group of Qi deficiency and Blood stasis and Water retention syndrome. Plasma metabolomic profiles were determined by UPLC-TOF/MS and analyzed by multivariate statistics. About 6 representative metabolites were highly possible to be associated with CHF, 4, 7, and 5 metabolites with Qi deficiency syndrome, Qi deficiency and Blood stasis syndrome, and Qi deficiency and Blood stasis and Water retention syndrome (VIP > 1, p < 0.05). The diagnostic model was further constructed based on the metabolites to diagnose other CHF patients with satisfying sensitivity and specificity (sensitivity and specificity are 97.1 and 80.6% for CHF group vs. NH group; 97.1 and 80.0% for QD group vs. NH group; 97.1 and 79.5% for QB group vs. NH group; 97.1 and 88.9% for QBW group vs. NH group), validating the robustness of plasma metabolic profiling to diagnostic strategy. By comparison of the metabolic profiles, 9 biomarkers, 2-arachidonoylglycerophosphocholine, LysoPE 16:0, PS 21:0, LysoPE 20:4, LysoPE 18:0, linoleic acid, LysoPE 18:2, 4-hydroxybenzenesulfonic acid, and LysoPE 22:6, may be especially for the effect of CHM granules. A predicting model was attempted to construct and predict patient based on the related symptoms of CHF and the potential biomarkers regulated by CHM were explored. This trial was registered with NCT01939236 (https://clinicaltrials.gov/).

Project description:BackgroundChronic heart failure (CHF) is a global public health problem. Therefore, novel and effective drugs that show few side-effects are needed. Early literature studies indicated that Huangqi injection is one of the most commonly used traditional Chinese patent medicines for CHF in China. As a large number of clinical studies has been carried out and published, it is essential to evaluate the effectiveness and safety of Huangqi injection. Therefore, we carried out this systematic review under the support of the framework of the Joint Sino-Italian Laboratory (JoSIL).ObjectivesTo evaluate the efficacy and safety of Huangqi injection for CHF according to the available scientific knowledge.MethodsAn extensive search including PubMed, EMBASE, CBM, the Cochrane Library and Chinese literature databases was performed up to July 2008. Clinical trials regarding Huangqi injection for the treatment of CHF were searched for, irrespective of languages. The quality of each trial was assessed according to the Cochrane Reviewers' Handbook 5.0, and RevMan 5.0 provided by the Cochrane Collaboration and STATA 9.2 were used for data analysis.ResultsAfter selection of 1,205 articles, 62 RCTs and quasi-RCTs conducted in China and published in Chinese journals were included in the review. The methodological quality of the trials was low. In most trials inclusion and exclusion criteria were not specified. Furthermore, only one study evaluated the outcomes for drug efficacy after an adequate period of time. For these reasons and because of the different baseline characteristics we did not conduct a meta-analysis.ConclusionsAlthough available studies are not adequate to draw a conclusion on the efficacy and safety of Huangqi injection (a traditional Chinese patent medicine), we hope that our work could provide useful experience on further studies on Huangqi injections. The overall level of TCM clinical research needs to be improved so that the efficacy of TCM can be evaluated by the international community and possibly some TCM can enter into the international market.

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Plasma metabonomics study on Chinese medicine syndrome evolution of heart failure rats caused by LAD ligation.

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Plasma metabonomics study on Chinese medicine syndrome evolution of heart failure rats caused by LAD ligation.

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