Anti-Acetylcholinesterase Activities of Mono-Herbal Extracts and Exhibited Synergistic Effects of the Phytoconstituents: A Biochemical and Computational Study

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.

Synthesis, In Silico and In Vitro Evaluation of Some Flavone Derivatives for Acetylcholinesterase and BACE-1 Inhibitory Activity

“…These two compounds have been used as references in many studies on AChE and BACE-1 inhibition. The results showed that the biological activities of the positive controls in this study are comparative to previously published values [ 34 , 35 , 36 ].…”

Synthesis, In Silico and In Vitro Evaluation for Acetylcholinesterase and BACE-1 Inhibitory Activity of Some N-Substituted-4-Phenothiazine-Chalcones

“…These two compounds have been used as references in many studies on AChE and BACE-1 inhibition. The results show that the biological activities of the positive controls in this study are comparative to the previously published values [ 56 , 57 , 58 ]. On the other hand, the experimental assays also specified that AC12 had a higher activity than galantamine on AChE and all the synthesized chalcones exhibited the higher inhibiting effects than quercetin on BACE-1.…”

Polyherbal Medicine Divya Sarva-Kalp-Kwath Ameliorates Persistent Carbon Tetrachloride Induced Biochemical and Pathological Liver Impairments in Wistar Rats and in HepG2 Cells

“…The traditional medicinal system is based on the application of polyherbal formulations. Pharmacological effects obtained from multiple plant extract metabolites are much higher as compared to single herb extracts (Yadav et al, 2008;Balkrishna et al, 2019a). In modern medicine, the treatment for chronic diseases has shifted from the "one drug, one target, one disease" paradigm toward combination therapies (Williamson, 2001;Zhou et al, 2016).…”