Molecular mechanism and therapeutic potential of YiQi FuMai injection in acute heart failure
Authors: Dai H , Li H S , Zhang J J , Chen Y , Zhang X C , Hu M Z , Guan Z Y , Liu Y , Shang H C 
Published: February 2022

Abstract

Funding Acknowledgements
Type of funding sources: Foundation. Main funding source(s): The National Science Foundation for Distinguished Young Scholars of China

Background
Acute heart failure (AHF) is a significant public health problem related to the high mortality and rehospitalization rate of patients. Although drug development is never interrupted, no single drug has been proven to play a decisive role in improving the survival of AHF patients. In China, multi-component traditional Chinese medicine has been widely used to treat AHF. As a Chinese herbal injection included in medical insurance, Yiqi Fumai Injection can reduce the level of NT-proBNP in AHF patients, improve heart function, and alleviate symptoms and signs related to heart failure. To further evaluate the therapeutic effect of Yiqi Fumai Injection on AHF, a multi-center, double-blind, randomized controlled trial that intends to recruit 1270 patients is being carried out in China. However, the mechanism of Yiqi Fumai Injection in the treatment of AHF has not been clarified. To further explore the underlying mechanism, we used systematic pharmacology methods to explore the potential molecular mechanisms of biologically active compounds.

Methods
We used the databases of HERB, the Encyclopedia of Traditional Chinese Medicine (ETCM), the Comparative Toxicogenomics Database (CTD), Online Mendelian Inheritance in Man (OMIM), and GeneCards to predict the active ingredients and potential targets of Yiqi Fumai Injection in the treatment of AHF. STRING was used for PPI network construction and analysis. Cytoscape was used to build a network between Chinese medicine, ingredients and targets. The DAVID, GO, and KEGG databases were used to predict the potential pathways of Yiqi Fumai Injection for the treatment of AHF.

Results
We obtained 31 active compounds of Yiqi Fumai Injection from HERB and ECTM databases. By overlapping targets between YQFMI and AHF, a total of 240 potential targets for Yiqi Fumai Injection to treat AHF were selected. According to the H-C-T network topology analysis, the core compounds include beta-sitosterol, Uridine, Guanosine, and Stigmasterol. Sixteen protein targets had significantly higher node degrees than the average in the PPI network, including AKT1, JUN, TNF, EDN1, CASP3, ESR1, DLG4, PTGS2, NOS3, IL1B, C3, AR, LEP, CNR1, CHRM2, and DRD2. The PPI results showed that the potential therapeutic targets of YQFMI were densely enriched in pathways related to endothelial function, neuromodulation, and lipid metabolism.The same results were shown in GO and KEGG pathway enrichment.

Conclusion
Our results indicate that Yiqi Fumai Injection may achieve the goal of improving AHF-related symptoms by regulating the function of vascular endothelium and nerves and the biosynthetic pathway of lipid metabolism. These findings support previous studies and provide a reference for studying the mechanism of Yiqi Fumai Injection in the treatment of AHF. Abstract Figure.