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Carthamus tinctorius is a medicinal herb containing various bioactive components implicated in antioxidative, antiinflammatory, antiviral, and neuroprotective effects, but the mechanisms underlying the neuroprotection is not known.In this study, we investigated the protective effects of Carthamus tinctorius extract on 6-hydroxydopamine (6-OHDA)-induced neurotoxicity in SH-SY5Y cell (a dopaminergic cell line).Our results showed that Carthamus tinctorius extract attenuated 6-OHDA-induced cell death in a dose-dependent manner, and decreased the elevated expression of Bax and active caspase-3 24 h after toxic insult.Carthamus tinctorius extract promoted an increase the activity of phosphatidilinositol-3 kinase/protein kinase B pathway.However, the presence of charybdotoxin or wortmanin (a PI3K inhibitor, 1 μM) completely blocked the neuroprotection and anti-apoptosis effect ofCarthamus tinctorius extract.Thus, activation ofphosphatidylinositol 3-kinase/protein kinase B pathway by Carthamus tinctorius extract mediates its neuroprotective effect on 6-OHDA-induced neurotoxicity.