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.
Highlights
Chronic heart failure (CHF) is a common, complex clinical syndrome that arises from structural or functional cardiac disorder, including changes in electrophysiology, contraction, and energy metabolism [1]
After pharmacologic interventions with Shenfu decoction (SFD) for 3 weeks, a significant improvement in left ventricular systolic pressure (LVSP), left ventricular end diastolic pressure (LVEDP), and ± dp/dtmax was observed compared with chronic heart failure (CHF) rats, without significant differences compared to sham and control groups
A GC/TOF–mass spectrometry (MS)-based metabolomic study was conducted to increase the understanding of CHF and assess the efficacy and mechanism(s) of SFD in treating CHF induced by coronary artery ligation in rats
Summary
Chronic heart failure (CHF) is a common, complex clinical syndrome that arises from structural or functional cardiac disorder, including changes in electrophysiology, contraction, and energy metabolism [1]. Heart failure (HF) is becoming an increasingly common diagnosis with an incidence approaching 10 per 1000 of the population over 65 years of age in developed countries [2]. The most effective and commonly used drugs for the treatment of HF are angiotensin-converting enzyme (ACE) inhibitors, β-adrenoceptor blockers, and digitalis [5,6,7]. TCMs such as Shengmai [9], Sini decoction [10], Shuanglong formula [11], and Huangqi injection [12] have potential therapeutic effects in the treatment of cardiovascular diseases
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