Tehran University of Medical Sciences Traditional and Integrative Medicine 2476-5104 11 2 2026 06 30 2207 2207 Kushani Perera Department of Life Sciences, NSBM Green University, Homagama, Pitipana, Sri Lanka AND Department of Chemistry, Faculty of Science, University of Kelaniya, Sri Lanka Yugani Rathnayake Department of Life Sciences, NSBM Green University, Homagama, Pitipana, Sri Lanka Thushani Madurangi Divisional Hospital, Maligawatte, Colombo 10, Sri Lanka 2025 06 29 2025 10 06 Crotalaria verrucosa L. (Fabaceae), or blue rattlepod, is a medicinal plant well-disseminated in tropical and subtropical areas and possesses a wide historical record of traditional use in medicine. Recent phytochemical and pharmacological investigations have revealed an intricate profile of bioactive secondary metabolites, including flavonoids, phenolic acids, terpenoids, phytosterols, and sapogenins, which exhibit impressive antioxidant, anti-inflammatory, hepatoprotective, and cytoprotective properties. This review critically synthesizes current knowledge on the botanical characteristics, phytochemical constituents, and pharmacological activity of C. verrucosa, focusing on its potential neuroprotective properties. Key constituents such as gallic acid, caffeic acid, catechin hydrate, vanillic acid, lupeol, and syringic acid act as reactive oxygen species scavengers and inhibitors of lipid peroxidation, thereby countering oxidative stress. Flavonoids, including (-)-epicatechin, vitexin, and isovitexin, are reported to activate the nuclear factor erythroid 2-related factor 2/antioxidant response element (Nrf2/ARE) pathway; while β-amyrin, β-sitosterol, and lupeol may influence phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) signaling. Compounds such as caffeic acid, syringic acid, lupeol, and stigmasterol demonstrate anti-inflammatory potential through nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and mitogen-activated protein kinase (MAPK) pathways modulation; whereas β-amyrin and β-sitosterol have been implicated in amyloid-β inhibition. Additional evidence suggests a role for phytosterols and sapogenins in cholinergic and GABAergic neurotransmission. Although these mechanistic insights are promising for neuroprotective actions, robust empirical validation in disease-specific in vivo and clinical models is still lacking. Therefore, future studies should prioritize bioactivity-guided fractionation, pharmacokinetics, and safety evaluation to advance C. verrucosa from traditional medicine toward modern drug discovery for neurodegenerative disorders. https://jtim.tums.ac.ir/index.php/jtim/article/view/2207