~1H NMR Based Metabonomic Study Of The Anti-heart Failure Effects Of Radix Astragali

Ethnopharmacology:In recent years, cardiovascular disease has become the leading causes of deach, among which heart failure (HF) is a critically illness. HF is high in mortality rate and its syndrome was described by reduced tissue and blood perfusion, pulmonary congestion or systemic congestion. Radix Astragali, a commonly used traditional Chinese medicine, has many effects such as strengthening Qi, diuresis, and anti-virus, which has been used for thousands of years in China to treat cardiovascular diseases. Astragali Radix is powerful in the treatment of HF, but the underlying mechanism is pooly understood, which need further invegestigations. Metabonomics is an important part of systems biology, with characteristics of integrated, dynamic, and sensitive in research methods, which makes it suitable for the study of complex systems of Chinese medicine since their similarity in ideology.Objective:The aim of this study is to systematilly analysis of metabolic characteristics and possible pathological mechanisms of HF, and explore the anti-heart failure mechanism of Radix Astragali. And further provide a scientific basis for its clinical application.Methods:1 HF model was made by intraperitoneal injection of doxorubicin, and the evaluation of Radix Astragali on HF was checked by various methods, including echocardiography, biochemical parameters, and pathological changes.2 1H NMR techniques combined with multivariate statistical analysis was used to detect bio-fluids (serum and urine) metabolic fingerprinting, and find potential biomarkers of HF. The regulation effects and the probable mechanism of Radix Astragali on HF was discussed.3 Myocardial metabonomics was applied to detect potential biomarkers related to HF and the regulation role of Radix Astragali. With the help of metabolic network analysis, the possible mechanism of Radix Astragali on heart failure was elucidated.Results:1 The HF model was confirmed by echocardiography, biochemical and histopathological results. Anti-heart failure effects of Radix Astragali differed with different doses:doses of 3.75 mg·kg-1 and 7.5 mg·kg-1 could improve cardiac systolic function and reduce myocardial injury of mild heart failure; when it was severe heart failure, dosage of 15 mg·kg-1 could play a satisfactory anti-heart failure effect.2 The serum metabonomics showed that 17 potential biomarnkers were related to DOX induced heart failure.In urine,8 potential biomarkers were identified. The disturbed pathways include fatty acids β-oxidation, ketone bodies metabolism, glucose metabolism, amino acid metabolism, methylamine metabolism, creatine metabolism, purine metabolism, and phenylalanine metabolism, among which purine metabolism in urine was first reported. In addition to purine metabolism, Radix Astragali was able to alleviate other metabolic pathway disorders.3 Myocardial metabonomics study showed that metabolic disorders of HF could be characterized by 15 metabolites, which involved in pathological processes such as lipid disorders, imbalance of energy metabolism, and oxidative stress. The protective effect of Radix Astragali was revealed by alleviating the metabolic network disturbances.Conclusion:HF model was simple in preparation, and high in success rate by intraperitoneal injection of doxorubicin. Radix Astragali is effective for the treatment of HF. Its action mechanism is closely correlated with improvement of myocardial energy metabolism, lipid metabolism, and inhibition of oxidative damage.