Screening Flavonoids for Inhibition of Acetylcholinesterase Identified Baicalein as the Most Potent Inhibitor

Abstract

Screening phenolic and polyphenolic compounds for inhibitory activity against electric eels acetylcholinesterase (AChE) identified baicalein, a major flavone derived from the roots of Scutellaria baicalensis, as the most potent inhibitor with IC50 (concentration required for 50% inhibition) of 0.61 µM. None of the hydroxybenzoic and hydroxycinnamic acids screened showed inhibitory activity measured at 100 µM. Structure-activity relationships based on IC50 values of the active flavonoids showed that inhibitory activity (a) required the unsaturated 2-phenyl-chroman structure, (b) has strong requirement for the A-ring A5-OH, A6-OH and A7-OH groups (b) does not depend on B-ring hydroxyl groups, and (d) was reduced by bulky sugar substitution of the saturated C-ring C3-OH. Enzyme kinetic analysis showed that baicalein is a mixed inhibitor of AChE with K 1 (equilibrium constant of dissociation of the inhibitor bound enzyme complex) and K 2 (equilibrium constant of dissociation of the inhibitor bound enzyme-substrate complex) of 0.91 and 1.98 µM, respectively.

The in vitro antioxidant properties ofMuscari comosumbulbs and their inhibitory activity on enzymes involved in inflammation, post-prandial hyperglycemia, and cognitive/neuromuscular functions

“…In particular, we found IC 50 value of 107.64 ± 5.38 (Table ) µg/mL, 12‐fold lower than galantamine (IC 50 of 8.97 ± 0.15 µg/mL), used as standard AChE inhibitor. The inhibition of the AChE by the extracts may be due to the phenolic compounds found in M. comosum bulb (Figure ), in particular flavonoids and phenolic acids that, according to some studies (Balkis, Tran, Lee, & Ng, ; Kim et al, ; Szwajgier, ), are able to inhibit AChE activity.…”

Cholinesterase targeting by polyphenols: A therapeutic approach for the treatment of Alzheimer’s disease

“…Multiple hydroxyl groups in the phenolic compound are believed to enhance the inhibitory action of AChE because of stronger binding capacity . These inhibitory actions explain the inhibitory potential of most of the phenolic compounds but not all follow the same mode of action . To summarize our article, different polyphenols and their mode of action have been listed in the Table .…”

“…Quercetin derivatives, such as quercetin‐3‐ O ‐(2′′,6′′‐di‐acetyl)‐glucoside (IC 50 = 36.47 μmol/L) and quercetin‐3‐ O ‐(2′′,6′′‐di‐rhamnosyl)‐glucoside (IC 50 = 94.92 μmol/L) extracted from this plant, are suggested to decrease the activity of AChE by binding with its active sites . The high potency of quercetin and its glucosides as AChE inhibitor has been reported in several other studies too …”

Nutritional properties, identification of phenolic compounds, and enzyme inhibitory activities of Feijoa sellowiana leaves

“…The highest enzymatic inhibition (92 ± 2.2%) was recorded at 1,000 µg/ml of FSLE, whereas the IC 50 value was only 120 µg/ml (Figure a). The high potency of FSLE to inhibit AChE might also be explained by its richness in quercetin derivatives, also reported to be potent with AChE inhibitors (Balkis, Tran, Lee, & Ng, ). However, the LB plot was used to study enzyme inhibition kinetics.…”

“…inhibitors (Balkis, Tran, Lee, & Ng, 2015). However, the LB plot was used to study enzyme inhibition kinetics.…”