Anti-aggregation effects of thymoquinone against Alzheimers -amyloid in vitro

Abstract

Beta amyloid peptide (Aβ) aggregation has been identified as one of the major causes of neurodegenerative processes in Alzheimer’s disease (AD). Despite recent improvements in the symptomatic therapy of cholinergic drugs; development of an effective therapeutic approach, that may interfere directly with Aβ aggregation in the central nervous system, is desperately required. Thymoquinone (TQ) is a bioactive compound isolated from Nigella sativa, which has been reported to be possessing various pharmacological attributes. The effects of TQ on the formation of Aβ1-40 were studied spectrophotometerically, over a duration of 16 days at pH 7.2 and 37°C. The inhibitory properties of TQ were compared with tannic acid (TA). Thymoquinone and TA, with IC50 of 0.1 and 29 µM at day 0 (within 5h), respectively, inhibited Aβ aggregation in a dose-dependent way at different concentrations, that is 1, 10 and 50 µM. However, at day 16, IC50 of TQ and TA were found to be 0.2 and 0.01 µM, respectively. In electron microscopic study, TQ, co-incubated with Aβ1-40, reduced the numbers of fibrils in some degree with shorter fibrils and small amorphous aggregates. Pretreated TQ protected cytotoxic effects of Aβ1-40 on primary cultured cerebellar granule neurons (CGNs). Therefore, TQ might have a direct interaction with Aβ resulting in prevention of Aβ aggregation and mediating its neuroprotective effects; thus may have potential in the therapeutic development of AD.\r\r\t \r\r\tKey words: Anti-aggregation, β-amyloid, thymoquinone, tannic acid, Alzheimer’s disease.