Lipid discovered in American ginseng alleviates doxorubicin-induced cardiotoxicity by inhibiting cardiomyocyte ferroptosis

心脏毒性 人参 阿霉素 生药学 传统医学 西洋参 药理学 医学 化学 生物 化疗 内科学 生物活性 生物化学 病理 体外 替代医学
作者
Kaiqing Hu,Huan Wang,Haiyang Wang,Taiping Li,Lu Liu,Haiyan Zhang,Zhenyu Li,Songsong Wang,Zhenyu Li
出处
期刊:Fitoterapia [Elsevier]
卷期号:177: 106097-106097 被引量:1
标识
DOI:10.1016/j.fitote.2024.106097
摘要

Doxorubicin (Dox)-induced cardiotoxicity (DIC) has limited its clinical application. It is crucial to discover more effective substances to treat DIC. In this study, a zebrafish model is used to evaluate the inhibition of DIC in the lipids in American ginseng (AGL) compared with the lipids in soybeans (SOL) and in egg yolks (YOL). A lipidomics approach based on Q Exactive LC-MS/MS is employed to monitor, identify, and analyze the lipid composition of three lipid samples. The H9c2 cell was used to investigate the key lipid in AGL for its effect mechanism in alleviating DIC. The results showed that AGL alleviated DIC on zebrafish by increasing the stroke volume, heart rate, and fractional shortening compared to SOL and YOL. A total of 216 differential lipids were identified among the three types of lipids using lipidomics. Besides, a fatty acid with 18 carbons and four double bonds, FA (18:4) was the dominant proportion in AGL and possessed the highest variable importance of projection (VIP) value. FA (18:4) also showed significant bioactivity to alleviate DIC in zebrafish. Furthermore, FA (18:4) reduced the ferric ions and reactive oxygen species (ROS) accumulation, increased GPX4 expression, and relieved mitochondrial damage to inhibit Dox-induced ferroptosis in H9c2 cells. Therefore, the composition characteristic and anti-DIC effect of AGL were revealed; FA (18,4) was identified for the first time to be a novel active component of AGL against DIC by inhibiting ferroptosis. These results provide a new understanding of AG-derived bioactive lipids and their potential benefits for heart health.
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