Kinetics and computational analysis of cholinesterase inhibition by REVERC3, a bisdemethoxycurcumin-rich Curcuma longa extract: Relevance to the treatment of Alzheimer’s disease

Abstract

Objectives: 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. Methods: 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. Results: 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 of REVERC3, 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. Conclusion: 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.

Discovery of pyrrole derivatives as acetylcholinesterase-sparing butyrylcholinesterase inhibitor

“…Therefore, non-competitive in combination with competitive inhibition and/or non-competitive in combination with anti-competitive inhibition maybe existed in the reaction systems of compound 3p with enzyme ( Figure 2B ). ( Hv et al, 2020 ) The above results indicated that compound 3p may combine with the free enzyme through the catalytic active sites (CAS) of enzyme to act as competitive inhibitors, or combine with enzyme together with substrate to act as non-competitive inhibiters, or directly interacte with the substrate-enzyme complex to act as anti-competitive inhibitors. However, the binding affinity of compounds 3p with the free enzyme or the substrate-enzyme complex was different.…”

Comparative Study of the Effects of Curcuminoids and Tetrahydrocurcuminoids on Melanogenesis: Role of the Methoxy Groups

“…The typical concentration of BDC (2-3%) in the regular turmeric extracts was enriched to 30-35% [12]. Other studies [77,79,80] have reported a much higher enrichment rate of 70-75% and demonstrated that these BDC-enriched extracts exhibited superior biological activity compared to conventional turmeric extracts. Based on the results of the current study, it is evident that BD has considerable potential in both mouse and human melanoma cells while having no discernible impact on normal human melanocytes.…”