Assessment of antioxidant, anticholinesterase and antiamyloidogenic effect of Terminalia chebula, Terminalia arjuna and its bioactive constituent 7-Methyl gallic acid - An in vitro and in silico studies

摘要

Alzheimer's disease is one of the most dreadful disorders of 21st century with no effective therapy till date, clinically characterized by loss of cognitive function. beta-amyloid peptide (A beta) is considered as the key pathogenic factor in AD, which on aggregation provokes oxidative stress mediated neuronal damage affecting activities of daily life such as learning and memory. Hence, the present study focuses on the exploration of neuroprotective potential of T. chebula and T. arjuna by evaluating its antioxidant, anticholinesterase and antiamyloidogenic activities. Results of antioxidant assays showed that methanolic extract of T. chebula fruit (TCF) and T. arjuna bark (TAB) exhibited highest reducing capacity, free radical scavenging activity and metal chelating potential. Furthermore, TCF and TAB also exhibited dual cholinergic effect by inhibiting both AChE (IC50 value 81.26 +/- 7.79 73.99 +/- 2.11 mu g/ml, respectively) and BuChE (IC50 value 81.44 +/- 1.23; 52.16 +/- 3.94 mu g/ml respectively). Total polyphenolic content of TCF and TAB was observed to be 479.25 +/- 0.5, 597.25 +/- 0.5 mu g of Gallic acid Equivalent/mg of extract. Molecular docking studies on LC-MS fractions of TCF and TAB revealed 7-MG as target compound with good predicted activities and promising ADMET properties. Enzyme kinetic studies revealed that 7-MG exhibited competitive and partially noncompetitive mode of inhibition for AChE and BuChE. Results of Th-T fluorescence, confocal microscopic and FTIR analysis illustrated that 7-MG blocked nucleation step thereby preventing the aggregation of A beta peptide and destabilizing the preformed mature fibrils. Over all the results conclude that 7-MG via its multi-targeting ability may be beneficial in the treatment of AD and related neurodegenerative disorders. (C) 2018 Elsevier B.V. All rights reserved.