ABUHAMDAH, RUSHDIE,MOHAMMED,ALI,SAID (2014) Chemical, molecular pharmacology and neuroprotective properties of the essential oil derived from
Aloysia citrodora Palau. Doctoral thesis, Durham University.
|PDF (PDF of the passed version of thesis full-text) - Accepted Version|
Essential oils derived from dried and fresh leaves of Aloysia citrodora were obtained by hydrodistillation, and were investigated for a range of pharmacological properties: receptor binding, in vitro acetylcholinesterase (AChE) inhibitory, antioxidant activities, and neuroprotection properties relevant to neurodegenerative diseases. Fresh leaf A. citrodora essential oil inhibited [3H] nicotine binding to well washed rat forebrain membranes, with mean apparent IC50 of 0.0018 mg/ml. No significant binding activity was observed for A. citrodora essential oil derived from fresh or dried leaves, for GABAAR and NMDARs. A. citrodora essential oil, both dried and fresh, exhibited radical scavenging activity (up to 100%, IC50 < 0.0001 mg/ml) and iron (II) chelating properties (approx. IC50 = 0.05 mg/ml), and showed neuroprotective characteristics against the toxic effects of H2O2 (100%, 0.001 mg/ml) and β-amyloid (approx. 50%, 0.01 mg/ml) in CAD neuronal cell culture. Both EOs from dried and fresh leaves also displayed effective AChE inhibitory activity, with the dried leaves oil displaying more clear AChE inhibitory activity than fresh oil, which could be related to the higher respective levels of caryophyllene oxide. Recombinant human anticholinesterase enzyme was used for structure based in silico screening of A. citrodora essential oil constituents for AChE Inhibitors, and the top scoring hits with highest pharmacophore fit values showed common interactions with residues at the active site of that of donepezil. The top seven hits in order of fit score, were β-curcumene, curcumene bisabolene, trans-calamenene, caryophyllene oxide, β-sesquiphellandrene and geranyl acetate. This indicates that plants may yield novel effective and safe AChE inhibitors, other than alkaloids. To begin to identify the chemicals underpinning the pharmacological properties of A. citrodora, GC/MS analysis of the chemical composition of the essential oil from leaves of A. citrodora identified eighty three major chemicals, including the presence of terpenoids, monoterpenes and sesquiterpenes, and 6-methyl-5-hepten-2-one, the main constituents being limonene, caryophyllene oxide, curcumene, spathulenol, 1,8-cineole constituting 47% of the total oil. Finally, a simple, inexpensive solid phase extraction method was developed for fractionation of essential oils. Collectively, this thesis provides a better understanding of the pharmacology of the Aloysia essential oil and its constituents relating to its potential use in the treatment neurodegenerative disease.
|Item Type:||Thesis (Doctoral)|
|Award:||Doctor of Philosophy|
|Keywords:||medicinal plants, phytochemistry, neurodegenerative diseases, neuroprotection, molecular pharmacology, modelling.|
|Faculty and Department:||Faculty of Science > Biological and Biomedical Sciences, School of|
|Copyright:||Copyright of this thesis is held by the author|
|Deposited On:||30 May 2014 10:30|