Deciphering the Molecular Mechanisms of QLQX Capsules in Heart Failure: A Multi-Omics Perspective

This study investigates the therapeutic mechanisms of Qiliqiangxin (QLQX) capsules in treating Heart Failure with Preserved Ejection Fraction (HFpEF). The study aims to understand how QLQX impacts cardiac function and underlying molecular pathways. HFpEF was induced in a rat model through unilateral nephrectomy, DOCA pellet implantation, and a high-salt diet. Cardiac function was assessed via M-mode imaging and Doppler flow measurements, focusing on key parameters like ejection fraction and diastolic function. A network pharmacology approach identified active QLQX components and potential targets, followed by comprehensive multi-omics analyses-including transcriptomics, proteomics, and metabolomics-to uncover the molecular mechanisms modulated by QLQX. Quantitative RT-PCR was employed to measure mRNA levels of key cardiac markers, providing further insights into QLQX's impact on cardiac remodeling. QLQX treatment significantly improved cardiac function, with notable enhancements in ejection fraction and left ventricular diastolic function. Network pharmacology revealed 530 potential targets of QLQX, with 38 overlapping HFpEF targets. Key pathways identified include cGMP-PKG, adrenergic signaling, and calcium signaling. Transcriptomic analysis showed significant gene expression changes related to inflammation, energy metabolism, and myocardial remodeling, which were reversed by QLQX. Proteomic analysis identified 401 differentially expressed proteins, enriched in pathways such as cGMP-PKG and NF-κB signaling. Metabolomic profiling highlighted the role of lipid metabolism and adrenergic signaling in HFpEF, which were normalized by QLQX. In vivo validation confirmed the involvement of the cGMP-PKG pathway, with increased serum NO and cGMP levels, improved endothelial function, and reduced pro-fibrotic markers following QLQX treatment. QLQX exerts multifaceted therapeutic effects on HFpEF by modulating gene expression, protein function, and metabolic pathways, particularly through the cGMP-PKG signaling pathway. These findings support QLQX as a promising therapeutic intervention for HFpEF, offering improvements in cardiac function and reversing pathological changes at multiple molecular levels.