RESUMEN
Background: Heart failure (HF) is a syndrome with global clinical and socioeconomic burden worldwide owing to its poor prognosis. Jiashen Prescription (JSP), a traditional Chinese medicine (TCM) formula, exhibits unambiguous effects on treating HF. Previously, we have reported that underlying mechanisms of JSP by an untargeted metabolomics approach, but the contribution of gut microbiota and metabolic interaction to the cardioprotective efficacy of JSP remains to be elucidated. Materials and methods: Firstly, the rat model of heart failure was established by the permanent ligation of the left anterior descending coronary artery. The efficacy evaluation of JSP in treating HF rats was per-formed by left ventricular ejection fraction (LVEF). Then, 16S rRNA gene sequencing and LC/MS-based metabolomic analysis were utilized to explore the characteristics of cecal-contents microecology and plasma metabolic profile, respectively. After that, the correlation between intestinal micro-ecological characteristics and plasma metabolic characteristics was analyzed to explore the potential mechanism of the JSP treatment in HF. Results: JSP could improve the cardiac function of heart failure rats and thus ameliorate heart failure via enhancing rat LVEF. Results of intestinal flora analysis revealed that JSP not only adjusted gut microbiota disturbances by enriching species diversity, reducing the abundance of pathogenic bacteria (such as Allobaculum, Brevinema), as well as increasing the abundance of beneficial bacteria (such as Lactobacillus, Lachnospiraceae_NK4A136_group), but also improved metabolic disorders by reversing metabolite plasma levels to normality. Through the conjoint analysis of 8 metabolites and the OTUs relative abundance data in the 16srRNA sequencing results by WGCNA method, 215 floras significantly related to the eight compounds were identified. The results of the correlation analysis demonstrated a significant association between intestinal microbiota and plasma metabolic profile, especially the significant correlation of Ruminococcaceae_UCG-014 and Protoporphyrin IX, Ruminococcaceae_UCG-005, Christensenellaceae_R-7_group and nicotinamide, dihydrofolic acid. Conclusion: The present study illustrated the underlying mechanism of JSP to treat heart failure by affecting intestinal flora and plasma metabolites, provide a potential therapeutic strategy against heart failure.
RESUMEN
Background: Heart failure is a chronic progressive condition that significantly affects the quality of life of patients with high hospitalization and mortality rates. Jiashen tablets (JST), a Chinese herbal formula, have been reported to be an effective treatment against heart failure, however the underlying mechanisms remain obscure. This study was designed to determine the effect of JST on the treatment of heart failure and delineate the underlying mechanisms by an untargeted metabolomics approach. Materials and methods: The chronic heart failure model was established by the permanent ligation of the left anterior descending coronary artery in rats. The cardiac functions of rats, including left ventricular ejection fraction (LVEF) and fractional shortening (LVFS), left ventricular internal diameter end diastole (LVIDd) and end systole (LVIDs), and interventricular septum thickness in diastole (IVSd) and in systole (IVSs), were measured by echocardiography. Biochemical analysis and histopathological examination were also performed to evaluate therapeutic effects of JST for treating heart failure. UHPLC-QTOF-MS/MS coupled with multivariate statistical analyses were applied for plasma metabolic profiling to identify biomarkers and potential mechanisms of JST in the treatment of heart failure. Results: Jiashen tablets could improve the cardiac function of heart failure rats and thus ameliorate heart failure via enhancing rat LVEF and LVFS and decreasing LVIDd, LVIDs, IVSd, and IVSs. Results of biochemical analysis and histopathological examination revealed that JST could reduce the serum lactate dehydrogenase (LDH) activity and the level of NT-pro BNP, markers of heart failure and myocardial damage, and inhibit myocardial fibrosis. Furthermore, in metabolomics analysis, a total of 210 metabolites with significant differences were identified between heart failure rats and normal rats, among which 29 metabolites were significantly restored after JST treatment. These metabolites were primarily involved in tryptophan metabolism, branched-chain amino acid metabolism, fatty acids ß-oxidation, and glycerophospholipid metabolism. Conclusion: The present study illustrated the therapeutic effect of JST for the treatment of heart failure and delineated the underlying mechanisms mainly relating to the regulation of amino acid metabolism and lipid metabolism in heart failure rats.