Dr Magdalini Papandreou was born and raised in Patras and received her BSc degree in Applied Biology from Staffordshire University in UK. In 2001, she was accredited training for Personal working under the Animals (Scientific Procedures) Act 1986 at Southampton University, while in 2002, she began her graduate studies (MSc) in Biochemical Pharmacology at the same university. Under the supervision of Professor Lindy Holden-Dye, she created GFP-labelled Caenorhabdidits elegans mutants and investigated the peptide content of pharyngeal neurons, with close attention to post-translational modifications, novel peptides and multiple gene products. In 2004, she enrolled at the University of Patras where she began her PhD studies in Biology. Under the supervision of the Assist. Professor Marigoula Margarity, she studied the possible neuroprotective properties afforded by Crocus species and their major isolated constituents on Alzheimer’s disease and ageing, both in vitro and in vivo, and obtained her Ph.D degree in 26/01/2010. During 2001-2002, she received a University Trust Bursary, from the CNS Inflammation Group at Southampton University, UK, where she was trained, under the supervision of Prof. Hugh Perry, on the role of acute phase proteins (APPs), and in particular, the pentraxins, in both acute and chronic neurodegeneration. She has also worked as a biochemistry laboratory assistant, at the Peripheral Academic Hospital of Rion, Patras, Greece, and as a microbiology assistant at the Laboratory of Special Mechanics, at the University of Patras, Greece, as part of her practical exercise. During her Ph.D. studies she has also assisted in teaching both undergraduate and graduate students modules like Animal Physiology I & II, Neurobiology and Experimental Physiology, and in their research projects that were under the supervision of the Assist. Professor M. Margarity, at the Laboratory of Human & Animal Physiology, University of Patras, Greece. She has published five articles in scientific journals with peer review system, while she also has other six published as supplements in National/International journals. She has received two scholarships from Onassis Public Benefit Foundation, one from Southampton University Trust Bursary and one from the Pharmaceutical Company GlaxoSmithKline S.A. She has participated in 11 International and 22 National Conferences, for which she has received two awards from the Hellenic Society of Neuroscience, one from the Federation of European Biochemistry Society (FEBS) and two from Aristides Daskalopoulos Foundation for her Ph.D. experimental work. She is an active member of the Hellenic Society of Biochemistry and Molecular Biology, the Hellenic Society of BioScience and the Hellenic Society of Neuroscience. On February 2012, her experimental work on blueberries and Alzheimer's disease was selected by the Ministry of Education, LifeLong Learning & Religious Affairs, for its «Academic and Scientific Excellence» and a tribute video was uploaded on: http://www.youtube.com/watch?v=3GsxgN3NVsE. In 2010 she was chosen to work as a Scientific collaborator at the Deputy office of the Minister of Education, LifeLong Learning & Religious Affairs, where she remained till May 2011. She was then appointed to GSRT (General Secretary of Research and Technology) where she continued to offer her services as a scientific collaborator, until June 2012.
Abstract: Inhibitors of acetylcholine breakdown by acetylcholinesterase (AChE) constitute the main therapeutic modality for Alzheimer's disease. In the search for natural products with inhibitory action on AChE, this study investigated the activity of saffron extract and its constituents by in vitro enzymatic and molecular docking studies. Saffron has been used in traditional medicine against Alzheimer's disease. Saffron extract showed moderate AChE inhibitory activity (up to 30%), but IC(50) values of crocetin, dimethylcrocetin, and safranal were 96.33, 107.1, and 21.09 μM, respectively. Kinetic analysis showed mixed-type inhibition, which was verified by in silico docking studies. Safranal interacts only with the binding site of the AChE, but crocetin and dimethylcrocetin bind simultaneously to the catalytic and peripheral anionic sites. These results reinforce previous findings about the beneficial action of saffron against Alzheimer's disease and may be of value for the development of novel therapeutic agents based on carotenoid-based dual binding inhibitors.
Abstract: Amyloid precursor protein (APP) altered metabolism, Aβ-overproduction/aggregation and oxidative stress are implicated in the development of Alzheimer's disease pathology. Based on our previous data indicating that administration of a polyphenol-rich (PrB) blueberry extract (from wild Vaccinium angustifolium) is memory enhancing in healthy mice and in order to delineate the neuroprotective mechanisms, this study investigated the antioxidant effects of PrB in H₂O₂-induced oxidative damage, Aβ peptide fibrillogenesis and APP metabolism. PrB suppressed H₂O₂-initiated oxidation (DCF assay) and cell death (MTT assay) in SH-SY5Y cells. Protective effects were observed on Chinese hamster ovary (CHO) cells overexpressing APP770 carrying the mutation Val717Phe only at high concentrations, while further damage on HEK293 cells was induced after co-treatment with 250 µM H₂O₂ and PrB in comparison with H₂O₂ alone. Using the thioflavine T assay, blueberry polyphenols inhibited Aβ-aggregation (~70%, 15 µg/mL) in a time-dependent manner, while in the CHO(APP770) cells it had no effect on APP metabolism as assessed by western blot. The results suggest that blueberry polyphenols exhibit antioxidant and/or pro-oxidant properties according to the cellular environment and have no effect on APP metabolism.
Abstract: Brain aging is characterized by cognitive decline and memory deficits that could be the result of oxidative stress and impaired cholinergic function. In this study, the effects of a daily, 7-day, intraperitoneal administration of saffron on cognitive functions were examined in both healthy adult (4 months old) and aged (20 months old), male Balb-c mice (n=8/group), by passive avoidance test. Whole brain homogenates (minus cerebellum) were collected for examination of brain oxidative markers, caspase-3 and acetylcholinesterase (AChE) activity. Results showed that saffron-treated mice exhibited significant improvement in learning and memory, accompanied by reduced lipid peroxidation products, higher total brain antioxidant activity and reduced caspase-3 activity in both age groups of mice. Furthermore, salt- and detergent-soluble AChE activity was significantly decreased only in adult mice. Thus, we showed, for the first time, that the significant cognitive enhancement conferred by saffron administration in mice, is more closely related to the antioxidant reinforcement. Next, we compared the effect of saffron (1-250μg/mL), crocetin and safranal (1-125μM) on H(2)O(2)-induced toxicity in human neuroblastoma SH-SY5Y cells. Both saffron and crocetin provided strong protection in rescuing cell viability (MTT assay), repressing ROS production (DCF assay) and decreasing caspase-3 activation. These data, together with earlier studies suggest that crocetin is a unique and potent antioxidant, capable of mediating the in vivo effects of saffron.
Abstract: The aim of this study was to examine the effect of a polyphenol-rich extract (PrB) of Vaccinium angustifolium (wild blueberries) introduced intraperitoneally (i.p.) at 30 (PrB30) and 60 (PrB60) mg/kg body weight for 7 days, on cognitive performance, brain oxidative status and acetylcholinesterase activity in adult, male, 3-4-month-old Balb-c mice. Evaluation of rodent learning and memory was assessed by a step-through test on day 6 after a double training and an initial acquisition trial on day 5. Antioxidant status was determined by ferric reducing antioxidant power (FRAP), ascorbic acid concentration (FRASC), malondialdehyde and reduced glutathione levels in whole brain homogenates. Acetylcholinesterase (AChE) activity was determined by Ellman's colorimetric method. Results showed that the PrB60-treated mice exhibited a significant improvement in learning and memory (step-through latency time of 228+/-38 s compared to 101+/-32 s of the control group). PrB extract administration also resulted in reduced lipid peroxidation products (38 and 79%) and higher brain ascorbic acid levels (21 and 64%) in both PrB30 and PrB60-treated groups, respectively, and higher glutathione levels (28%) in the PrB60-treated group. Furthermore, salt- and detergent soluble AChE activity significantly decreased in both PrB-treated groups. Thus, the significant cognitive enhancement observed in adult mice after short-term i.p. supplementation with the blueberry extract concentrated in polyphenols, is closely related to higher brain antioxidant properties and inhibition of AChE activity. These findings stress the critical impact of wild blueberry bioactive components on brain function.
Abstract: Crocus sativus stigmas are one of the widely known spices (saffron) and consist of unusually polar carotenoids. Alzheimer's disease is characterized pathologically by deposition of amyloid beta-peptide (Abeta) fibrils. Oxidation is thought to promote Abeta fibril formation and deposition. To identify agents inhibiting the pathogenesis of Alzheimer's disease, we examined in vitro the antioxidant properties of extract of C. sativus stigmas and its effect on Abeta(1-40) fibrillogenesis. The antioxidant properties were determined by measuring the ferric-reducing antioxidant power and Trolox-equivalent antioxidant capacity, while its effects on Abeta-aggregation and fibrillogenesis were studied by thioflavine T-based fluorescence assay and by DNA binding shift assay. The water:methanol (50:50, v/v) extract of C. sativus stigmas possesses good antioxidant properties, higher than those of tomatoes and carrots, and inhibited Abeta fibrillogenesis in a concentration and time-dependent manner. The main carotenoid constituent, trans-crocin-4, the digentibiosyl ester of crocetin, inhibited Abeta fibrillogenesis at lower concentrations than dimethylcrocetin, revealing that the action of the carotenoid is enhanced by the presence of the sugars. Our findings suggest the possible use of C. sativus stigma constituents for inhibition of aggregation and deposition of Abeta in the human brain.
