Olive biophenols: a natural beta-secretase (BACE-1) inhibitor

Globally growing public health concern, Alzheimer disease (AD) affecting a high percentage of people over age 65 years including Australia. The exact cause of the AD is still unknown but the evidence suggests that the ageing and family history. Currently, there is no treatment and cure for AD but the symptomatic relief drug will delay the disease progression. According to the most accepted amyloid hypothesis, the extracellular deposits of amyloid beta peptide (Aβ) which is produced from sequential endoproteolytic cleavage of amyloid precursor protein (APP) by β- and γ-secretases. Biophenols are the naturally accruing secondary phenol content metabolites of ubiquitous presence in the plant kingdom. Studies have been showed that the biophenols regulate Aβ production and clearance, it has been suggested that a few biophenols act by directly inhibiting β-secretase (BACE-1) activity. In the present study, we have investigated the direct inhibitory effects of olive biophenols including flavonoids (quercetin, rutin, luteolin), non-flavonoids (oleuropein, hydroxytyrosol, verbascoside, caffeic acid) and commercial extracts (olive leaf and fruit extract). Mostly of the olive biophenols significantly inhibited in vitro BACE-1 activity measured by using fluorometer with an excitation wavelengths of 335-345 nm and emission wavelengths of 485-510 nm). The flavonoid biophenol, rutin showing the highest BACE-1 inhibition (IC50 3.8nM) followed by non-flavonoid biophenol verbascoside (IC50 6.3nM)). The major biophenol among the olive leaf and fruit, oleuropein showed inhibition (IC50 2.76µM) followed by another major compound hydroxytyrosol (IC50 35nM). The commercial olive extracts also showed significant inhibition, olive fruit extract showed the highest (IC50 18ng) followed by hydroxytyrosol extreme extract ((IC50 0.26µg). Taken together, our data suggested that the olive biophenols could be promising compound against Aβ production in the development of Alzheimer's disea