Key result
Fuzheng Yixin decoction improves cardiac function and attenuates ventricular remodeling in DCM rats via sGC-cGMP-PKG signaling.
Why the study?
The therapeutic effects and underlying mechanisms of Fuzheng Yixin decoction in doxorubicin-induced dilated cardiomyopathy were not fully understood.
In a rat model of doxorubicin-induced dilated cardiomyopathy, Fuzheng Yixin decoction demonstrated cardioprotective effects potentially mediated through the restoration of the sGC-cGMP-PKG signaling pathway.
FZYX effects in rat DCM models remain preliminary; leaves open translation to human therapy.
OBJECTIVE: To investigate the effect of Fuzheng Yixin decoction (, FZYX) and explore its underlying mechanisms in doxorubicin-induced dilated cardiomyopathy (DCM) rat model. METHODS: Sprague-Dawley rats were intraperitoneally injected with doxorubicin for 6 consecutive weeks. Ultra-high-perform ance liquid chromatography Q-exactive mass spectrometry was utilized to obtain mass spectrum data for FZYX. The rats were then intragastrically injected with low-dose FZYX, high-dose FZYX, or captopril for 4 weeks. Serum N-terminal pro-brain natriuretic peptide, transthoracic echocardiography, haematoxylin and eosin and Masson staining, electron microscopy, and immunohistochemistry were used to evaluate the efficacy of FZYX. Differentially expressed genes and metabolites in the myocardial tissue of DCM rats following FZYX intervention were subsequently identified through transcriptomics and non-targeted metabolomics. Finally, the influence of FZYX on the expression of natriuretic peptide precursor A (Nppa), natriuretic peptide precursor B (Nppb), soluble guanylyl cyclase (sGC), protein kinase G (PKG), and PKG-1α in DCM rats was verified through quantitative polymerase chain reaction (qPCR), Western blotting (WB) based on the results of transcriptomics and non-targeted metabolomics analyses. RESULTS: FZYX alleviated body weight loss; inhibited ventricular dilatation; restored impaired heart function, ruptured sarcomeres and mitochondrial damage, and pathological changes; and reduced collagen deposition. Transcriptomic and non-targeted metabolomic results revealed that FZYX regulated the expression of sGC-cyclic guanosine monophosphate (cGMP)-PKG pathway-related genes (Nppa, Nppb) and metabolites such as cGMP, 5'-guanylic acid, adenosine. qPCR and WB demonstrated that FZYX suppressed the expression of Nppa and Nppb and increased the expression of sGC, which led to a further increase in the level of PKG and PKG-1α. CONCLUSION: These findings suggest that the cardioprotective effect of FZYX may be mediated through the restoration of the sGC-cGMP-PKG signaling pathway. FZYX may provide a new strategy for clinical application against DCM.
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Sang et al. (2026) studied Doxorubicin-induced dilated cardiomyopathy (DCM). Fuzheng Yixin decoction (FZYX) vs. captopril was evaluated on Cardiac function, pathological changes, and expression of sGC-cGMP-PKG pathway-related genes and metabolites. Fuzheng Yixin decoction restored impaired heart function, inhibited ventricular dilatation, and reduced collagen deposition in DCM rats, likely via the sGC-cGMP-PKG signaling pathway.
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