Pharmacology of Olive Biophenols in Alzheimer's Disease Prevention and Treatment

    Research output: ThesisDoctoral Thesis

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    Changes in normal protein conformation followed by accumulation cause
    neurodegenerative disease, among them Alzheimer’s disease (AD) is the most prevalent, complex and multifactorial neurodegenerative condition. AD is a progressive dementia characterised by the deposition of senile plaques (amyloid beta) and neurofibrillary tangles (tau protein) leading to neuronal degeneration accompanied by a decline in cognition and memory. In addition, complex pathology of AD includes oxidative stress, metal deposition (iron and copper), alteration in enzymes such as cholinesterase, betasecretase, tyrosinase and histone deacetylase. The current therapeutic targets include the enzymes involved in the formation or degradation of the amyloid and tau proteins.
    Accumulating evidence suggests that diet may play an important role in lowering the risk of developing AD. From the epidemiological studies, Mediterranean diet has received major attention because of its association with low incidence of cardiovascular diseases, cancers and other age-related chronic diseases. Amongst the chief constituents of the Mediterranean diet are olives and their virgin oil.

    Studies have suggested that pharmacological activities in olive are attributed to its biophenolic constituents. Biophenols are universal plant constituents that have attracted scientific attention due to their multiple pharmacological properties including their antioxidant activities. Olive biophenols are attracting public and commercial interest due to a number of health claims. Thus, there is an increasing number of olive fruit and olive leaf extracts that have been introduced to the health market as nutraceuticals or food supplements. My work is an extension of more than 18 years of research on olive biophenols at Charles Sturt University. I am trying to move the focus beyond antioxidant activities of biophenols and linking antioxidant activity with other pharmacological activities. My aim is to understand the mechanism of action of olive biophenols in combating AD. My research adopts a holistic approach where I have tried to investigate the activities of olive biophenols at the molecular, cellular, tissue and functional levels. I have also paid special attention to make understanding the activity of individual biophenols versus their combined activity in biophenol extracts.

    In the present study, the phenolic content and antioxidant activities of four commercial olive extracts have been investigated. The bioactivities of the extracts have been compared with the bioactivities of major olive biophenolic constituents viz. hydroxytyrosol, caffeic acid, oleuropein, verbascoside, quercetin, luteolin, and rutin. The enzyme inhibitory activity of olive biophenols have been investigated against four enzymes involved in the pathology of AD. The anti-amyloid activities of olive biophenols have been further investigated in a number of assays. Furthermore, the neuroprotective activities of olive biophenols were assessed against four neurotoxic substances in
    neuroblastoma cells (SH-SY5Y). Finally, olive biophenols have been evaluated in
    amyloid precursor protein Swedish transgenic mice (APPswe) to assess their potential to work in vivo. Both biochemical changes and behavioural changes were evaluated after chronic administration of olive biophenol extracts.
    Original languageEnglish
    QualificationDoctor of Philosophy
    Awarding Institution
    • Charles Sturt University
    • Obied, Hassan, Principal Supervisor
    • Scott, Chris, Co-Supervisor
    • Hamlin, Adam, Co-Supervisor
    Award date01 Mar 2015
    Place of PublicationAustralia
    Publication statusPublished - 2015


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