Promoting tissue repair with plant-derived compounds: evidence and mechanisms from zebrafish studies

The pursuit of strategies to enhance tissue repair is a central challenge in regenerative medicine, where plant-derived compounds offer immense therapeutic potential due to their multi-target, systems-level activities. Validating and mechanistically deciphering these pro-repair effects requires robust, predictive, and ethically tractable in vivo models. The zebrafish (Danio rerio) has emerged as a preeminent model that powerfully bridges this gap. This review synthesizes the growing body of literature utilizing zebrafish injury models to evaluate the therapeutic potential of herbal extracts and their active constituents. We detail the application of zebrafish models for external wound healing (caudal fin and skin injury), internal tissue repair (bone and vasculature), and chemical-induced organ damage (heart and liver). The collective evidence demonstrates that plant-derived compounds promote repair across these diverse paradigms by modulating evolutionarily conserved mechanisms, including inflammation, oxidative stress, apoptosis, autophagy, and key developmental signaling pathways such as Wnt/β-catenin and NF-κB. The unique advantages of the zebrafish-including optical transparency for real-time imaging, genetic tractability, and high physiological conservation with humans-make it an indispensable platform for high-throughput screening and deep mechanistic inquiry. By translating the complex pharmacology of botanicals into actionable insights within a living vertebrate system, zebrafish research accelerates the discovery and validation of the health-promoting effects of natural compounds, firmly establishing their role in tissue regeneration and illuminating a clear path toward their development as next-generation regenerative therapies.