Exploring the effective components and mechanism of Shengmaiyin (Dangshen Prescription) on the treatment of chronic heart failure based on chinmedomics strategy.

Abstract

Shengmaiyin (Dangshen Prescription, SMY) is a well-known traditional Chinese medicine prescription used for chronic heart failure (CHF) patients, whereas its pharmacodynamic material basis and mechanisms remain insufficiently elucidated. This study aimed to identify the effective components and investigate the mechanisms of SMY against CHF utilizing the chinmedomics approach. First, a CHF rat model was established through multiple low-dose doxorubicin injections. The therapeutic efficacy of SMY was evaluated through histopathological analysis, echocardiographic assessment, serum biochemical measurements and serum metabolic profiling. The chinmedomics strategy was then employed to screen the effective components and explore the therapeutic mechanisms. Finally, the experiments of malondialdehyde (MDA), superoxide dismutase (SOD) and terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL) were applied to further confirm the metabolisms. The results indicated SMY significantly alleviated CHF symptoms, as evidenced by restored cardiac function indices and decreased serum levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) and tumor necrosis factor-α (TNF-α). A total of 27 serum metabolite biomarkers were identified, 19 of which were significantly reversed following SMY treatment. These biomarkers were associated with disturbances in amino acid and lipid metabolism. Moreover, 16 serum migrant constituents were identified, and 9 of those, namely 5-Hydroxymethylfurfural (5-HMF), codonopsinol B, ruscogenin, lobetyolin, schizandrol A, codonopsine, schisantherin B, codonopiloside A, schizandrol B were validated as effective components. The therapeutic effects of SMY on CHF might be mediated through the regulation of apoptosis and oxidative stress. This study provides the first comprehensive elucidation of the therapeutic mechanisms and effective components of SMY in the treatment of CHF.