IDENTIFICATION OF SMALL MOLECULE INHIBITORS AGAINST AMYLOID β (Aβ) OLIGOMERIZATION AND TOXICITY FROM NOOTROPIC AYURVEDIC HERBAL EXTRACTSAbstract
Central pathogenic mechanism of Alzheimer’s disease (AD) involves aggregation of amyloid β (Aβ) protein to form toxic oligomers. Identifying novel small molecules that inhibit the aggregation of monomeric Aβ to toxic oligomeric species can be an effective disease modifying strategy for AD. In the present study, plants being used in Ayurveda for treating dementia as well as to improve memory and cognitive function have been considered. These included Nelumbo nucifera, Valeriana wallichii, Celastrus paniculatus, and Raulfia serpentina. We tested the efficacy of these plant extracts and some of their active ingredients for their anti-amyloidogenic property by means of in vitro aggregation studies. The effect of each extract or phytocompound was tested on inhibition of aggregation as well as dissociation of preformed aggregates using thioflavin T fluorescence assay and transmission electron microscopy. Of the compounds screened, β-sitosterol and valerenic acid prevented the aggregation of Aβ while α-asarone and glycyrrhizin were effective in dissociating the preformed aggregates. More importantly, all the four phytocompounds have conferred protection against Aβ mediated toxicity in rat primary hippocampal cultures. These substances may hold therapeutic potential for AD treatment.
Maya Mathew, B.K. Chandrasekhar Sagar and Sarada Subramanian*
Additional Professor, Department of Neurochemistry, National Institute of Mental Health & Neurosciences, Bangalore – 560 029, Karnataka, India
23 July, 2013
14 August, 2013
20 November, 2013
01 December 2013