Except for clinical value, borneol is routinely used in food and cosmetics with seldom safety evaluation. To investigate its hepatoxicity, we exposed 3 dpf (days post fertilization) larval zebrafish to borneol at a gradient of concentrations (200–500 μM) for 3 days. Herein, our results revealed that high doses of borneol (300–500 μM) caused liver size decrease or lateral lobe absence. Borneol also seriously disturbed the hepatic protein metabolism presented with the increased activity of alanine aminotransferase (ALT) and lipid metabolism shown with the increased level of triglycerides (TG) and total cholesterol (TC). The lipid accumulation (oil red staining) was detected as well. Additionally, significant upregulation of genes was detected that related to oxidative stress, lipid anabolism, endoplasmic reticulum stress (ERS), and autophagy. Conversely, the lipid metabolism-related genes were markedly downregulated. Moreover, the changes in the superoxide dismutase activity and the level of glutathione and malondialdehyde raised the likelihood of lipid peroxidation. The outcomes indicated the involvement of oxidative stress, ERS, lipid metabolism, and autophagy in borneol-induced lipid metabolic disorder and hepatic injury. This study will provide a more comprehensive understanding of borneol hepatoxicity and the theoretical basis for the safe use of this compound.

Seven main ginsenosides, including ginsenoside Re, ginsenoside Rb1, pseudoginsenoside F11, ginsenoside Rb2, ginsenoside Rb3, ginsenoside Rd and ginsenoside F2, were identified by LC-QTOF MS/MS from root, leaf and flower extracts of Panax quinquefolius. These extracts promoted intersegmental vessel growth in a zebrafish model, indicating their potential cardiovascular health benefits. Network pharmacology analysis was then conducted to reveal the potential mechanisms of ginsenoside activity in the treatment of coronary artery disease. GO and KEGG enrichment analyses elucidated that G protein-coupled receptors played a critical role in VEGF-mediated signal transduction and that the molecular pathways associated with ginsenoside activity are involved in neuroactive ligand-receptor interaction, cholesterol metabolism and the cGMP–PKG signaling pathway, etc. Moreover, VEGF, FGF2, and STAT3 were confirmed as the major targets inducing proliferation of endothelial cells and driving the pro-angiogenic process. Overall, ginsenosides could be potent nutraceutical agents that act to reduce the risks of cardiovascular disease. Our findings will provide a basis to utilize the whole P. quinquefolius plant in drugs and functional foods.

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