Study on the mechanism of Xinmailong injection against chronic heart failure based on transcriptomics and proteomics

Xinmailong (XML), a traditional Chinese medicine derived from Periplaneta americana, is commonly used in China to treat chronic heart failure (CHF). However, its pharmacological mechanism remains unclear. In our research, we employed Doxorubicin (Dox) to create a CHF animal model and administered XML treatment to investigate the pharmacological effects of XML on CHF rats by combining transcriptomic and proteomic analyses. XML improved dox-induced CHF and improved cardiac function, and a joint multi-omics analysis demonstrated that it reduced cardiomyocyte fibrosis during CHF. There is further evidence that XML may alleviate cardiomyocyte fibrosis through its effects on the cGMP-PKG signaling pathway or by reducing the expression levels of COL1A1, COL3A1, MMP9, and CXCR2. In this study, the effects of XML on rats with CHF are examined at the transcriptional and protein levels, as well as its mechanism and mode of action in treating CHF. There may be novel therapeutic targets or clinical indications for XML-based CHF therapy resulting from the study's identification of significant differential genes and signaling pathways. • In this study, we used transcriptomics and proteomics approaches to investigate the potential mechanism of XML for improving CHF in rats. Our findings indicate that differential genes expression and the cGMP-PKG signaling pathway play critical roles in the development and progression of CHF and that XML may help treat CHF by regulating crucial gene expression and activating the cGMP-PKG signaling pathway. This will facilitate the individualization and accurate usage of this drug in the clinic, as well as improve its social and economic benefits. • We investigated the mechanism of Xinmailong injection in CHF rats at the transcript level and discovered that it may reduce cardiomyocyte fibrosis by lowering COL1A1, COL3A1, MMP9, and CXCR2 expression levels and restore cardiac function in rats with chronic heart failure. This is thought to be a novel target for Xinmailong injectable treatment of CHF. • The significance of our research lies in its potential to advance the understanding of CHF and open new avenues for the development of therapeutic strategies. Proteomics screening of critical proteins and the cGMP-PKG signaling pathway, which play important roles in CHF development and cardiovascular disease management, are likely to reveal new therapeutic targets.