Novel Anti-Acetylcholinesterase Effect of Euonymus laxiflorus Champ. Extracts via Experimental and In Silico Studies

Abstract

Alzheimer’s disease (AD) is the most common form of dementia, which is recorded as a global health issue. Natural acetylcholinesterase inhibitors (AChEIs) are considered a helpful therapy for the management of symptoms of patients with mild-to-moderate AD. This work aimed to investigate and characterize Euonymus laxiflorus Champ. (ELC) as a natural source of AChEIs compounds via in vitro and virtual studies. The screening parts used, including the leaves, heartwood, and trunk bark of ELC, revealed that the trunk bark extract possessed the highest activity, phenolics and flavonoid content. The in vitro anti-Alzheimer activity of ELC trunk bark was notably reclaimed for the first time with comparable effect (IC50 = 0.332 mg/mL) as that of a commercial AChEI, berberine chloride (IC50 = 0.314 mg/mL). Among various solvents, methanol was the most suitable to extract ELC trunk bark with the highest activity. Twenty-one secondary metabolites (1–21) were identified from ELC trunk bark extract, based on GCMS and UHPLC analyses. Of these, 10 volatile compounds were identified from this herbal extract for the first time. One phenolic (11) and seven flavonoid compounds (15–21) were also newly found in this herbal extract. Of the identified compounds, chlorogenic acid (11), epigallocatechin gallate (12), epicatechin (13), apigetrin (18), and quercetin (20) were major compounds with a significant content of 395.8–2481.5 μg/g of dried extract. According to docking-based simulation, compounds (11–19, and 21) demonstrated more effective inhibitory activity than berberine chloride, with good binding energy (DS values: −12.3 to −14.4 kcal/mol) and acceptable RMSD values (0.77–1.75 Å). In general, these identified compounds processed drug properties and were non-toxic for human use, based on Lipinski’s rule of five and ADMET analyses.

Assessment of the Chemical Profile and Potential Medical Effects of a Flavonoid-Rich Extract of Eclipta prostrata L. Collected in the Central Highlands of Vietnam

“…These results suggest that salicylic acid and wedelolactone play significant roles in the anti-AChE activity of the EPL extract. In addition, the high AChE inhibition potential may be due to the high levels of epicatechin gallate, myricetin, isovitexin, apigetrin [54,55] components in the EPL extract. These components also exhibit a high ability to inhibit AChE, as indicated by their IC 50 values presented in Table 6.…”

“…Lipinski's Rule of Five has been wildly utilized for evaluating the drug-likeness of an inhibitor compound when considering its further development as a drug [54,64,65]. Lipinski's Rule of Five includes "mass < 500 Da, LogP value < 5, H-donor linkages < 5, H-acceptors linkages < 10, and the molar refractivity values in the range of 40-130".…”

“…The flow rate was maintained at 0.2 mL/min throughout the analysis, and the gradient program was set as follows: 0.0-0.5 min, 5% MeOH; 0.5-8.0 min, 5-30% MeOH; 8.0-13 min, 30-45% MeOH; 13.0-18.0 min, 45-65% MeOH; 18.0-22.0 min, 65-95% MeOH; and 22.0-26.0 min, 95-5% MeOH. The injection volume was 2 µL, and peaks were monitored simultaneously at 265 nm [54,68,69].…”

Plant-Derived Natural Products and Their Biomedical Properties: Recent Advances and Future Directions

“…Euonymus laxiflorus Champ. (ELC), a Vietnamese medicinal plant already known for its antioxidant and antidiabetic activity, has been investigated for its anti-acetylcholinesterase effect, an important mechanism for the management of Alzheimer's disease [3]. Interestingly, the ELC trunk bark extract featured a high phenolic and flavonoid content, and its in vitro anti-acetylcholinesterase activity was comparable to that of berberine chloride, a known acetylcholinesterase inhibitor.…”

“…Interestingly, the ELC trunk bark extract featured a high phenolic and flavonoid content, and its in vitro anti-acetylcholinesterase activity was comparable to that of berberine chloride, a known acetylcholinesterase inhibitor. The compounds with the highest concentration included chlorogenic acid, epigallocatechin gallate, epicatechin, apigetrin, and quercetin, while docking-based simulations revealed their potential drug properties due to their significant binding energy to acetylcholinesterase [3].…”