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Article Publish Status: FREE
Abstract Title:

Kinetics and computational analysis of cholinesterase inhibition by REVERC3, a bisdemethoxycurcumin-richextract: Relevance to the treatment of Alzheimer's disease.

Abstract Source:

SAGE Open Med. 2020 ;8:2050312120973499. Epub 2020 Nov 23. PMID: 33282298

Abstract Author(s):

Sudeep Hv, Amritha Raj, Gouthamchandra K, Chandrappa S, Shyamprasad K

Article Affiliation:

Sudeep Hv

Abstract:

Cholinesterase inhibition is a common strategy to treat Alzheimer's disease. In this study, we have investigated the cholinesterase inhibitory effects of a first-of-its-kind turmeric extract (REVERC3) having enriched content of bisdemethoxycurcumin as major active curcuminoid.: The inhibition studies were performed using Ellman's colorimetric assay. The kinetics of acetylcholinesterase and butyrylcholinesterase was determined in the presence of REVERC3 using the Lineweaver-Burk double reciprocal plots. Furthermore, we used AutoDock tools to predict the binding of bisdemethoxycurcumin with the active sites of cholinesterases.: REVERC3 showed 4.8- and 5.39-fold higher inhibitory potential of acetylcholinesterase and butyrylcholinesterase with IC50 values of 29.08 and 33.59 µg/mL, respectively, compared to the regular turmeric extract. The mode of binding of REVERC3 was competitive in the case of acetylcholinesterase while it was uncompetitive for the inhibition of butyrylcholinesterase. Docking analysis revealed that bisdemethoxycurcumin, the major constituent ofREVERC3, has different preferences of binding in the active sites of acetylcholinesterase and butyrylcholinesterase. However, the best binding pose predictions are in line with the experimental binding mode of the cholinesterases.: These results indicate that bisdemethoxycurcumin-enriched turmeric extract could improve the cholinergic functions via dual inhibition of cholinesterases. However, the predominant role of bisdemethoxycurcumin in REVERC3 must be further validated using preclinical studies and clinical trials.

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