Neuroprotective effects of green tea (Camellia sinensis) and broccoli (Brassica oleracea) extracts against Cuprizone‑induced cytotoxicity in neuroblastoma (SH‑SY5Y) cells

Abstract Background Natural antioxidants are crucial in slowing the progression of nervous system disorders such as multiple sclerosis (MS), primarily by counteracting oxidative stress and neuroinflammation-two central drivers of neuronal injury. Green tea (EGCG) and broccoli (sulforaphane, SF) extracts are rich in potent antioxidant and anti‑inflammatory compounds, yet their comparative neuroprotective efficacy against cuprizone (CPZ)‑induced toxicity has not been thoroughly investigated. Methods GC–MS confirmed catechins and caffeine as the main green tea constituents, and sulforaphane with flavonoids as predominant in broccoli. SH‑SY5Y neuroblastoma cells were exposed to CPZ (750 or 1000 µM) with or without extract pretreatment (EGCG, 5 or 10 µM; SF, 10 or 20 µM). Cell viability (MTT, trypan blue), membrane/nuclear morphology (light and fluorescence microscopy), and expression of MMP‑3, IL‑1β, NF‑κB1, HIF‑1α, and miR‑124‑3p were assessed. Results CPZ (750 µM) reduced viability by > 80% and induced marked structural damage. Optimal doses—EGCG 5 µM and SF 10 µM—significantly preserved cell viability and morphology. CPZ elevated MMP‑3 and suppressed NF‑κB1, HIF‑1α, and miR‑124‑3p, with no change in IL‑1β. EGCG alone markedly reduced MMP‑3 and IL‑1β; SF alone lowered IL‑1β and moderated miR‑124‑3p loss. SF + CPZ broadly attenuated CPZ effects, significantly reducing MMP‑3 and IL‑1β and restoring NF‑κB1 and HIF‑1α. EGCG + CPZ conferred selective protection but increased MMP‑3 relative to EGCG alone. Conclusion Both extracts mitigate CPZ‑induced neurotoxic signaling via distinct yet overlapping pathways—EGCG through targeted suppression of matrix degradation, SF through broader anti‑inflammatory and gene‑restorative effects. The current findings support their potential as complementary neuroprotective strategies, warranting further in vivo validation.