Identification of key pharmacodynamic markers of American ginseng against heart failure based on metabolomics and zebrafish model

作者：Rong Dong, Yougang Zhang, Shanjun Chen, Huan Wang, Kaiqing Hu, Huanxin Zhao, Qingping Tian, Ke‐Wu Zeng, Songsong Wang, Liwen Han · 发表于：Frontiers in Pharmacology · 年份：2022 · DOI：10.3389/fphar.2022.909084 · 被引用次数：32 · 研究领域：Ginseng Biological Effects and Applications、Traditional Chinese Medicine Analysis、Lipid metabolism and disorders

Background: American ginseng ( Panax quinquefolium L., AG) is a traditional Chinese medicine with multiple cardiovascular protective properties. Many bioactive components have been discovered in AG over these years. However, the understanding of these key pharmacodynamic components of activity against heart failure is insufficient. Methods: A heart failure model was established using AB line wild-type zebrafish ( Danio rerio ) to evaluate the anti-heart failure activity of AG. Untargeted metabolomics analysis based on ultra-high performance liquid chromatography-quadrupole electrostatic field orbitrap-mass spectrometry technology (UHPLC-QE-Orbitrap-MS) was performed to screen differential components from AG samples. The potential active components were verified using the zebrafish model. Simultaneously, network pharmacology and molecular docking techniques were used to predict the possible mechanism. Finally, the key targets of six key pharmacodynamic components were verified in zebrafish using quantitative real-time-polymerase chain reaction (Q-PCR) techniques. Results: The heart failure model was successfully established in 48 h of post-fertilization (hpf) zebrafish larvae by treating with verapamil hydrochloride. The zebrafish assay showed that the anti-heart failure effects of AG varied with producing regions. The result of the herbal metabolomic analysis based on UHPLC-QE-Orbitrap-MS indicated that ginsenoside Rg3, ginsenoside Rg5, ginsenoside Rg6, malic acid, quinic aci...