Cardioprotective Mechanism and Active Compounds of on Adriamycin-Induced Cardiotoxicity: A Network Pharmacology Study.

OBJECTIVE

To investigate the mechanism of (FG) against adriamycin-induced cardiotoxicity (AIC) through a network pharmacology approach.

METHODS

Active ingredients of FG were screened by TCMSP, and the targets of active ingredient were collected by Genclip3 and HERB databases. AIC-related target genes were predicted by Genecards, OMIM, and CTD databases. Protein-protein interaction (PPI) network was constructed by STRING platform and imported into Cytoscape software to construct the FG-active ingredients-targets-AIC network, and CytoNCA plug-in was used to analyze and identify the core target genes. The Metascape platform was used for transcription factor, GO and signaling pathway enrichment analysis.

RESULTS

27 active ingredients of FG and 1846 potential targets were obtained and 358 AIC target genes were retrieved. The intersection of FG and AIC targets resulted in 218 target genes involved in FG action. The top 5 active ingredients with most targets were quercetin, luteolin, kaempferol, isorhamnetin, and sesamin. After constructing the FG-active ingredients-targets-AIC network, CytoNCA analysis yielded 51 core targets, of which the top ranked target was STAT3. Ninety important transcription factors were enriched by transcription factor enrichment analysis, including RELA, TP53, NFKB1, SP1, JUN, STAT3, etc. The results of GO enrichment analysis showed that the effective active ingredient targets of FG were involved in apoptotic signaling, response to growth factor, cellular response to chemical stress, reactive oxygen species metabolic process, etc. The signaling pathway enrichment analysis showed that there were many signaling pathways involved in AIC, mainly including pathways in cancer, FOXO signaling pathway, AGE-RAGE signaling pathway in diabetic complications, signaling by interleukins, and PI3K-AKT signaling pathway,.

CONCLUSIONS

The study based on a network pharmacology approach demonstrates that the possible mechanisms of FG against AIC are the involvement of multicomponents, multitargets, and multipathways, and STAT3 may be a key target. Further experiments are needed to verify the results.