Ayurvedic Neuroprotective Phytochemicals and Their Evaluation in Zebrafish Models: Pharmacological Insights and Translational Challenges

Ayurvedic medicine has been traditionally employed for the management of numerous neurological and psychological disorders through the use of medicinal plants enriched with biologically active phytochemicals. Several Ayurvedic herbs possess flavonoids, alkaloids, tannins, sterols, glycosides, and polyphenolic compounds that exhibit antioxidant, anti-inflammatory, neuroprotective, anxiolytic, and cognition-enhancing activities. Recent advances in experimental neuroscience have identified zebrafish (Danio rerio) as an efficient vertebrate model for investigating central nervous system (CNS) disorders and evaluating neuroactive compounds because of its genetic homology with humans, conserved neurotransmitter pathways, rapid embryonic development, and suitability for high-throughput screening. This review summarizes the CNS related pharmacological effects of important Ayurvedic medicinal plants, including Withania somnifera (L.) Dunal, Bacopa monnieri (L.) Wettst., Curcuma longa L., Centella asiatica (L.) Urb, Ocimum tenuiflorum L., and Clitoria ternatea L., with particular emphasis on their assessment in zebrafish models. Evidence from experimental studies indicates that these herbal interventions demonstrate neuroprotective, anti-stress, anxiolytic, anti-amnesic, and locomotor-regulating effects in zebrafish models of neurological dysfunction. Nevertheless, limitations associated with extract standardization, mechanistic validation, and interspecies translational variability continue to restrict clinical extrapolation. Furthermore, the review discusses the translational relevance of zebrafish in understanding molecular, behavioral, and neurochemical mechanisms associated with Ayurvedic therapies. Important challenges, including variability in phytochemical composition, dose standardization, pharmacokinetic limitations, species-specific metabolic differences, and safety concerns, are also critically evaluated. In addition, the potential integration of nanotechnology-based delivery systems with Ayurvedic medicines is highlighted as a promising strategy for improving bioavailability and therapeutic efficacy. Collectively, zebrafish models represent a valuable experimental platform for advancing Ayurvedic neuropharmacology and translational CNS drug discovery.