Hippophae rhamnoides L. is a deciduous shrub that contains many unique bioactive substances. This sea buckthorn possesses anticancer, antioxidant, anti-inflammatory, and cardiovascular protective properties. Herein, the effects of phenylpropyl compounds extracted from H. rhamnoides L. on doxorubicin (Dox)-induced cardiotoxicity were evaluated in zebrafish. Cardiac injury in zebrafish was induced using 35 μM Dox for 96 h, and 30 μM phenylpropanoid compounds were used as the protective treatment. The cardioprotective effects and mechanisms of the four phenylpropanoids were investigated using microscopy, behavioral analysis, acridine orange staining, western blotting, flow cytometry, and real-time quantitative polymerase chain reaction. The extracted phenylpropanoids could significantly relieve Dox-induced cardiac injury in zebrafish and inhibit cardiomyocyte apoptosis. The mechanisms of action were mainly related to the stability of mitochondrial biogenesis and function maintained by phenylpropanoids in zebrafish. To our knowledge, this is the first report on the protective effect of sea buckthorn against myocardial injury in zebrafish. Our findings provide support for the further research and development of sea buckthorn and its components.

Background: The metabolic dysfunction-associated steatotic liver disease (MASLD) represents an escalating global health concern, with effective treatments still lacking. Given its complex pathogenesis, multi-targeted strategies are highly desirable. Methods: This study reports the isolation of four flavone C-glycosides (FCGs) from Dianthus superbus L. and explores their potential in treating MASLD. The bioactivity and underlying mechanisms of FCGs were systematically evaluated by integrating network pharmacology, molecular docking, and zebrafish model validation. Results: Network pharmacology analysis revealed that FCGs may modulate multiple MASLD-related pathways, including lipid metabolism, insulin signaling, inflammation, and apoptosis. Molecular docking further confirmed strong binding affinities between FCGs and key protein targets involved in these pathways. In the zebrafish model of MASLD induced by egg yolk powder, FCGs administration markedly attenuated obesity, hepatic lipid accumulation, and liver tissue damage. Furthermore, FCGs improved lipid metabolism and restored locomotor function. Molecular analyses confirmed that FCGs upregulated PPARγ expression to promote lipid metabolism, restored insulin signaling by enhancing INSR, PI3K, and AKT expression, and suppressed inflammation by downregulating TNF, IL-6 and NF-κB. Additionally, FCGs inhibited hepatocyte apoptosis by elevating the BCL-2/BAX ratio. Conclusions: These findings highlight the multi-pathway regulatory effects of FCGs in MASLD, underscoring its potential as a novel therapeutic candidate for further preclinical development.