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
| Autor: | Rajamohamed Beema Shafreen, Natarajan Suganthy, Arivalagan Pugazhendhi, Kasi Pandima Devi |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Antioxidant medicine.medical_treatment Pharmacology medicine.disease_cause Neuroprotection 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Materials Chemistry medicine Gallic acid Physical and Theoretical Chemistry IC50 Spectroscopy biology Chemistry Condensed Matter Physics biology.organism_classification Atomic and Molecular Physics and Optics Electronic Optical and Magnetic Materials Terminalia chebula 030104 developmental biology Polyphenol Terminalia arjuna 030217 neurology & neurosurgery Oxidative stress |
| Zdroj: | Journal of Molecular Liquids. 257:69-81 |
| ISSN: | 0167-7322 |
| DOI: | 10.1016/j.molliq.2018.02.081 |
| Popis: | 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. β-amyloid peptide (Aβ) 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 μg/ml, respectively) and BuChE (IC50 value 81.44 ± 1.23; 52.16 ± 3.94 μg/ml respectively). Total polyphenolic content of TCF and TAB was observed to be 479.25 ± 0.5, 597.25 ± 0.5 μg 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 Aβ 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. |
| Databáze: | OpenAIRE |
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