Punica granatum (pomegranate) outer tissues, particularly peel and pericarp fractions, represent a chemically rich but underutilized reservoir of bioactive phytoconstituents with significant therapeutic relevance. Recent research has increasingly focused on valorizing agricultural waste streams for biomedical applications, especially in aquatic vertebrate models such as zebrafish and other small ichthyic systems that enable rapid functional screening of phytochemical effects. This review synthesizes current knowledge on the phytochemical composition, mechanistic bioactivity, and experimental validation of Punica-derived compounds in small fish systems, emphasizing integrated botanical profiling and physiological response evaluation.

The primary objective is to consolidate evidence regarding antioxidant, neuroactive, anti-inflammatory, and metabolic regulatory properties of Punica outer tissue extracts, and to interpret their functional relevance in vertebrate aquatic models. Particular attention is given to mechanistic parallels between plant-derived polyphenolic activity and vertebrate pharmacodynamic responses, as well as the role of model fish systems in bridging in vitro phytochemistry with in vivo functional outcomes. Studies consistently indicate that pomegranate peel extract (PPE) contains ellagitannins, flavonoids, and phenolic acids capable of modulating oxidative stress pathways, neuronal signaling cascades, and metabolic regulation.

Findings across experimental systems demonstrate that Punica-derived compounds influence behavioral endpoints such as locomotor activity, anxiety-like responses, and stress adaptation in fish models, suggesting neurochemical modulation at the organismal level. These effects are frequently associated with changes in antioxidant enzyme activity and neuroinflammatory markers. Integrated evidence highlights the importance of dose-dependent pharmacodynamic responses and environmental sensitivity in aquatic organisms exposed to plant-derived bioactives.

This review further contextualizes these findings within broader pharmacological modeling frameworks and comparative biochemical systems biology. It emphasizes the translational potential of Punica residue valorization in biomedical research and environmental toxicology. The synthesis aligns with experimental findings reported in recent zebrafish-based investigations demonstrating significant neurobehavioral and phytochemical interactions of PPE, reinforcing its role as a multifunctional bioactive system (Agarwal & Usharani, 2026; Agarwal & Usharani, 2026; Agarwal & Usharani, 2026).