Zebrafish as a translational platform for investigating multi-organ pharmacological interactions of traditional...

The advancement of Traditional Chinese Medicine (TCM) requires model systems capable of dissecting its multi-component, multi-target pharmacology in a rapid and systematic manner. This review presents the zebrafish as a versatile in vivo pharmacological platform for modern TCM research, not merely a screening tool. We synthesize its recent applications across cardiovascular, neuropsychiatric, metabolic, and oncological diseases, emphasizing how optical transparency and genetic tractability enable real-time quantification of multi-target interactions - for instance, dose-dependent heart rate changes, neutrophil migration distances, and tumor fluorescence intensities - thereby linking molecular pathways to whole-organism phenotypic outcomes. A dedicated section critically evaluates its role in mechanistic safety assessment, moving beyond descriptive toxicology toward elucidation of adverse outcome pathways. We then identify current limitations where the zebrafish's potential is underutilized, such as in resolving the spatiotemporal dynamics of herbal formula compatibility. Finally,we propose "zebrafish-plus" paradigms integrating organoids, single-cell multi-omics, and AI-driven phenotypic analytics. These frameworks are designed to generate testable mechanistic hypotheses and perform early efficacy/safety profiling, while explicitly recognizing that all zebrafish-derived findings require rigorous validation in mammalian models before clinical interpretation.