Research

My research interests are divided into two related fields namely blood-brain barrier (BBB) and the discovery of neuroprotective agent for the treatment of Parkinson’s disease (PD).

Blood-brain barrier:
Blood-brain barrier (BBB) is a vascular barrier formed at the level of brain capillary endothelial cells (BCEC). Expression of complex tight junctions impede the paracellular permeability of small charged molecules including nutrients and physiological ions such as glucose, amino acids and sodium. Expression of various carrier-mediated transporters and ion channels assist in two-way transport of these molecules (blood-to-brain vs brain-to-blood). Lipophilic compounds can easily permeate through the BCEC lipid bilayer, however, high expressions of efflux pumps at the BBB essentially extrude most of the lipophilic compounds en-route to the brain. The formation of BBB is the evolutionary strategy to maintain the optimum ionic concentration of brain interstitial fluid (ISF) for neuronal communications and signalling. Despite the importance of BBB in maintaining the optimum environment by avoiding rapid fluctuations of solutes content in brain ISF, it also impedes delivery of drug target for central nervous system (CNS) such as drugs for the treatment of Parkinson’s disease, brain tumour, pain and drug addiction. My research interest is therefore to manipulate various transport mechanisms at the BBB through chemical modification of drug or using nanocarrier to enhance brain penetration of potential CNS drug candidates. Brain permeability parameters like rate and extent of brain permeation of potential CNS drugs are obtained by in situ brain perfusion experiment in rodents which can also be used to obtain information on the mechanisms of brain uptake.

Parkinson’s disease:
Parkinson’s disease (PD) is the second most frequent neurodegenerative disease in the world. As the population of older people increase due to improvement of living standard, so does the population of PD. Current primary treatment with levodopa (L-DOPA) focusses on improvement of symptomatic PD without delaying dopaminergic neuron cell death in the basal ganglia. Treatment with L-DOPA comes with side effects with the most prominent one is L-DOPA induced dyskinesia (LID). L-DOPA will also not be effective when most of dopaminergic neurons have loss. Currently, there are no single effective neuroprotective agent for PD in the clinic to delay or stop dopaminergic neurons death in the basal ganglia. Therefore, my research interest is to screen the potential neuroprotective compounds in in vitro and in vivo models of PD. Currently available are chemically synthesised β-carboline derivatives and isolated flavonoids from Pteridophytes (edible fern).

People

Publications

SELECTED PUBLICATIONS (FROM 2010)

1. Joseph, A., Contini, C., Cecchin, D., Nyberg, S., Ruiz-Perez, L., Gaitzsch, J., Fullstone, G., Tian, X., Azizi, J., Preston, J., Volpe, G., Battaglia, G. (2017) Chemotactic synthetic vesicles: Design and applications in blood-brain barrier crossing. Sci Adv. 3, e1700362Sci Adv. 3, e1700362.
2. Azizi, J., Ismail, S., Mansor, S.M. (2013) Mitragyna speciosa Korth leaves extracts induced the CYP450 catalyzed aminopyrine-N-demethylase (APND) and UDP-glucuronosyl transferase (UGT) activities in male Sprague-Dawley rat livers. Drug Metabol Drug Interact. 28, 95.
3. Azizi, J., Ismail, S., Mordi, M.N., Ramanathan, S., Said, M.I., Mansor, S.M. (2010) In vitro and in vivo effects of three different Mitragyna speciosa korth leaf extracts on phase II drug metabolizing enzymes--glutathione transferases (GSTs). Molecules. 15, 432.
4. Hanapi, N. A., Azizi, J., Ismail, S., Mansor, S. M. (2010) Evaluation of selected Malaysian medicinal plants on phase I drug metabolizing enzymes, CYP2C9, CYP2D6 and CYP3A4 activities in vitro. International Journal of Pharmacology, 6, 494.

Published Abstracts

1. Ismail, S., Hanapi, N.A., Azizi, J., Mansor, S.M., Mahmud, R. (2010) Inhibition of human cytochrome P450 isoforms by Mitragyna speciosa extracts. Drug Metabolism Reviews 42, 144. 9th International Meeting of the International-Society-for-the-Study-of-Xenobiotics (ISSX).