Plant biophenols have been shown to be effective in the modulation of Alzheimer's disease (AD) pathology resulting from free radical-induced oxidative stress and imbalance of the redox chemistry of transition metal ions (e.g., iron and copper). On the basis of earlier reported pharmacological activities, olive biophenols would also be expected to have anti-Alzheimer's activity. In the present study, the antioxidant activity of individual olive biophenols (viz. caffeic acid, hydroxytyrosol,

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... opein, verbascoside, quercetin, rutin and luteolin) were evaluated using superoxide radical scavenging activity (SOR), hydrogen peroxide (H 2 O 2 ) scavenging activity, and ferric reducing ability of plasma (FRAP) assays. The identification and antioxidant activities in four commercial olive extracts-Olive leaf extract TM (OLE), Olive fruit extract TM (OFE), Hydroxytyrosol Extreme TM (HTE), and Olivenol plus TM (OLP)-were evaluated using an on-line HPLC-ABTS •+ assay, and HPLC-DAD-MS analysis. Oleuropein and hydroxytyrosol were the predominant biophenols in all the extracts. Among the single compounds examined, quercetin (EC 50 : 93.97 µM) and verbascoside (EC 50 : 0.66 mM) were the most potent SOR and H 2 O 2 scavengers respectively. However, OLE and HTE were the highest SOR (EC 50 : 1.89 µg/mL) and H 2 O 2 (EC 50 : 115.8 µg/mL) scavengers among the biophenol extracts. The neuroprotection of the biophenols was evaluated against H 2 O 2 -induced oxidative stress and copper (Cu)-induced toxicity in neuroblastoma (SH-SY5Y) cells. The highest neuroprotection values (98% and 92%) against H 2 O 2 -induced and Cu-induced toxicities were shown by the commercial extract HTE TM . These were followed by the individual biophenols, caffeic acid (77% and 64%) and verbascoside (71% and 72%). Our results suggest that olive biophenols potentially serve as agents for the prevention of neurodegenerative diseases such as AD, and other neurodegenerative ailments that are caused by oxidative stress. Aβ-induced neurotoxicity in AD [2] . Evidence suggests that the production of ROS supports the "oxidative stress hypothesis" of AD [3] . In addition, metal ions induce the Aβ itself to produce the ROS, in turn causing oxidative stress-induced neurotoxicity [4] . Metal ions, such as iron and copper, that promote the formation of free radicals via the Fenton reaction, were observed to increase neurotoxicity in AD [5] . Importantly, these elevated markers for oxidative stress precede Aβ deposition and neurofibrillary tangles, suggesting that oxidative stress is an "early event" in AD pathogenesis. The endogenous antioxidant defense system is based on both enzymatic (superoxide dismutase, catalase, and glutathione peroxidase) reactions and non-enzymatic reactions involving compounds such as vitamins C and E, β-carotene, uric acid, and glutathione. These are found within the cytoplasm and various cell organelles to counter free radicals [6] . Apart from the aforementioned endogenous antioxidants, the secondary metabolites of plants, known as biophenols, have received considerable attention as exogenous antioxidants in the last two decades [7] . It has been proposed that the consumption of fruit and vegetable juices, containing high concentrations of biophenols, at least three times per week may delay the onset of AD [8] . A number of studies have reported the daily biophenol consumption in a number of European countries, including Finland (863 ± 415 mg/day) [9], France (1193 ± 510 mg/day) [10], Spain (820 ± 323 mg/day) [11] , and Poland (1756.5 ± 695.8 mg/day) [12] . A Japanese study reported biophenol consumption at 961 ± 452 mg/day in an elderly population [13] . All these studies used the Phenol-Explorer database [14] or similar sources containing quantitative values measured by HPLC methods [15] . Indeed, increasing evidence suggests that the non-vitamin antioxidants, such as the biophenols, which show pleiotropic activity, including ROS scavenging and chelation of transition metals, especially iron and copper, are currently attracting considerable interest as potential therapeutic agents to counteract diseases, including AD, that are associated with oxidative stress [16] . Olive (Olea europaea L.) biophenols are an important component of the Mediterranean diet, and have received much attention due to their antioxidant effects [17] . A number of studies have suggested that the consumption of a traditional Mediterranean diet is associated with the reduction in the incidence of cardiovascular diseases, certain cancers and improved cognition [18] [19] [20] . The main phenolic compounds found in olive fruit are hydroxytyrosol (3) and tyrosol (2) respectively [21], while oleuropein (4) represents the major biophenol in olive leaf [22] , followed by other constituents verbascoside (6), luteolin-7-O-glucoside, apigenin-7-O-glucoside, and tyrosol (2) [23] . The antioxidant activities of various olive preparations, both in vitro and in vivo, have been attributed to the biophenols, principally oleuropein (OL), hydroxytyrosol (HT), oleuropein aglycone (OA) and verbascoside (VB) [17] . Moreover, the activities of OL and HT were found to be higher than the well-known antioxidants, vitamins E and C. Perhaps surprisingly, tyrosol is reported as displaying neither antioxidant nor pro-oxidant activity [24] . Olive leaf extract also showed higher antioxidant activity than either vitamin C or vitamin E [25] . A limited number of cell line studies have reported the antioxidant activity of olive biophenols [26] [27] [28] . To the best of our knowledge, no study investigating the neuroprotective activity of olive biophenols in neuroblastoma (SH-SY5Y) cells has been carried out. As part of our continuing efforts at developing a dietary biophenols-based strategy targeting oxidative stress-induced cellular toxicity, we submit the present study to elucidate further the antioxidant capacity of olive biophenols (individually and as extracts) in cell-free as well as in an in vitro model of AD in SH-SY5Y cells. Accordingly, we determined the total phenols content (TPC) and total flavonoids content (TFC) of four commercial olive preparations.