Abstract
Alzheimer’s disease (AD), a neurodegenerative disease, is the most common form of dementia. Inhibition of acetylcholinesterase (AChE) is a common strategy for the treatment of AD. In this study, aqueous, hydro-methanolic, and methanolic extracts of five potent herbal extracts were tested for their in vitro anti-AChE activity. Among all, the Tinospora cordifolia (Giloy) methanolic fraction performed better with an IC50 of 202.64 µg/mL. Of the HPLC analyzed components of T. cordifolia (methanolic extract), palmatine and berberine performed better (IC50 0.66 and 0.94 µg/mL, respectively) as compared to gallic acid and the tool compound “galantamine hydrobromide” (IC50 7.89 and 1.45 µg/mL, respectively). Mode of inhibition of palmatine and berberine was non-competitive, while the mode was competitive for the tool compound. Combinations of individual alkaloids palmatine and berberine resulted in a synergistic effect for AChE inhibition. Therefore, the AChE inhibition by the methanolic extract of T. cordifolia was probably due to the synergism of the isoquinoline alkaloids. Upon molecular docking, it was observed that palmatine and berberine preferred the peripheral anionic site (PAS) of AChE, with π-interactions to PAS residue Trp286, indicating that it may hinder the substrate binding by partially blocking the entrance of the gorge of the active site or the product release.
Highlights
Alzheimer’s disease (AD) is a neurodegenerative disease and is the most common form of dementia in elderly people worldwide [1,2]
Earlier reports have shown that the stronger inhibitory activity of alkaloids is associated with their similarity to ACh, and many alkaloids have positively-charged nitrogen which can bind in the gorge of active sites of AChE [20]
Palmatine was 0.66 μg/mL (1.93 μM), whereas the IC50 of berberine was 0.94 μg/mL (2.80 μM); both the Studies show that berberine exhibits beneficial effects in AD through inhibition on both AChE and inhibitors showing stronger interaction as compared galantamine hydrobromide
Summary
Alzheimer’s disease (AD) is a neurodegenerative disease and is the most common form of dementia in elderly people worldwide [1,2]. Tacrine (CognexTM), the first FDA-approved medicationfor AD, was an AChE inhibitor. It was withdrawn from the market because of its hepatotoxicity [8]. AChE inhibitors are donepezil (AriceptTM), rivastigmine (ExelonTM), and galantamine (ReminylTM), which were approved in 1996, 2000, and 2001, respectively [9,10]. Galantamine and rivastigmine are plant derived alkaloids Among these inhibitors, Donepezil is the only AChE inhibitor approved for the treatment of all stages of AD [8,9,10]. In this work, we have studied comparatively the three different fractions (aqueous, hydro-methanolic, and methanolic) of five potent anti-acetylcholinesterase herbal extracts; that is why the outcome of this work could be useful for lead compound identification for cognitive function improvement in AD
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