Discovery of key lipids from Panax quinquefolius against doxorubicin-induced cardiotoxicity based on a zebrafish model

Abstract Objective To discover novel pharmacodynamic substances from Panax quinquefolius against doxorubicin (Dox)-induced cardiotoxicity using a zebrafish model. Methods AB line zebrafish embryos at 30h post-fertilization (hdf) were exposed to Dox (30 µM) for 42h and the heart rate, stroke volume, cardiac area, and fractional shortening of larval zebrafish were used to assess cardiotoxicity. The lipid sample from Panax quinquefolius (PQL) was evaluated the protection of doxorubicin- induced cardiotoxicity compared with the lipids from soybean (SOL) and egg yolk (YOL). The three lipids were analysed using lipidomics techniques based on Q Exactive LC-MS/MS to screen differential lipids. The key lipid was verified the activity against doxorubicin- induced cardiotoxicity using the zebrafish model. Results PQL could significantly alleviate the Dox-induced the decreased heart rate, decreased stroke volume, and decreased fractional shortening (%) on the zebrafish model. 216 differential metabolites were identified, among which the unsaturated fatty acids were the crucial difference components between the three lipid samples. The 18 carbon fatty acids with four carbon–carbon double bonds (FA (18:4)) had been identified and be as a remarkable active compound with protection of Dox-induced cardiotoxicity on the zebrafish model. Conclusion In this research, PQL was discovered firstly to exhibit notable activity against Dox-induced cardiotoxicity in zebrafish, and FA (18:4) was identified as a novel key active component from PQ.