Neuritogenic effects of Ulva lactuca aqueous extract on Neuro-2a cells

Full abstract

Read the full abstract

BACKGROUND: Neurodegenerative diseases are characterized by progressive neuronal loss and impaired neural connectivity, and effective strategies to promote neuronal regeneration remain limited. In particular, there is a lack of well-characterized neuritogenic agents, highlighting the need for novel candidates. Marine-derived natural products have garnered attention owing to their structural diversity and biological activities. Ulva lactuca, a green macroalga rich in bioactive compounds such as sulfated polysaccharides and phenolics, exhibits various biological effects; however, its neuritogenic potential has not been systematically investigated. METHODS: N2a cells were treated for 48 h with graded concentrations of aqueous U. lactuca extract, either alone or in combination with nerve growth factor (NGF), to evaluate neuritogenic activity. Cell viability was assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, while neurite outgrowth was quantified by counting neurite-bearing cells. Neuronal differentiation was further evaluated using α-tubulin immunofluorescence staining. RESULTS: The extract significantly enhanced N2a cell viability and neurite outgrowth at optimal concentrations. Treatment with 5 mg/mL extract increased the proportion of neurite-bearing cells by 8.51%, which was further increased to 14.21% in combination with NGF. In contrast, higher concentrations (≥ 10 mg/mL) of the extract attenuated neuritogenic responses, indicating a biphasic dose-dependent effect. CONCLUSIONS: These findings suggest that the aqueous extract of U. lactuca may contain bioactive constituents capable of promoting neurite initiation and elongation in vitro. At appropriate concentrations, U. lactuca extract can serve as a potential natural source for neuritogenic agents, warranting further investigation into its underlying mechanisms and active components.