Objective: Achillea millefolium ( A. millefolium ) is a traditional herbal medicine that contains natural compounds with antioxidant activities and is used for a wide range of conditions among people. The aim of our study was to investigate antioxidant and anti-acetylcholinesterase activities of A. millefolium extracts to determine its potential therapeutic usage in Alzheimer’s disease (AD). Methods: Methanol extracts (ME) and ethanol extracts (EE) of A. millefolium were prepared to determine (a) in vitro antioxidant activities, (b) the effects on acetylcholinesterase kinetics (by using a colorimetric spectroscopic method) and (c) the effects on sodium nitroprusside (SNP)-induced lipid peroxidation in mice brain homogenate. Results: ME had higher antioxidant activities compared to EE. Both extracts displayed a competitive inhibition of acetylcholinesterase; however, the inhibitory activity of ME was higher than EE. The inhibitory constant (K _i ) values of ME and EE were found to be 28.43 and 68.47 μg/mL, respectively. Both extracts caused a significant concentration-dependent decrease in malondialdehyde (MDA) contents in mice brain homogenate, indicating a strong inhibition of lipid peroxidation. Conclusions: Our results showed that A. millefolium has a high antioxidant capacity and anti-acetylcholinesterase activity due to its phenolic compounds, suggesting a potential use as adjuvant therapy in neurodegenerative conditions such as AD.

The scope of this study was to investigate the total phenolic, anthocyanin, and flavonoid contents and the biological properties of ethanol extract (EE), methanol extract (ME), and aqueous extract (AE) from Vaccinium arctostaphylos L. EE, ME, and AE of V. arctostaphylos were prepared. Various biological activities such as total phenolic, anthocyanin, and flavonoid contents, and antioxidant (2,2'-diphenyl-1-picrylhydrazyl ferrous ion-chelating, and ferric reducing antioxidant power assays), α-glucosidase inhibitory, anti-inflammatory, and DNA protective properties of these extracts were studied. EE exhibited the highest total phenolic, anthocyanin, and flavonoid contents with 44.42±1.22 mg gallic acid equivalents/g dry weight, 8.46±0.49 mg/Cyaniding-3-glucoside equivalents/g dry weight, and 9.22±0.92 mg quercetin equivalents/g dry weight, respectively. The antioxidant activities of the extracts followed the order: EE>ME>AE. EE and ME inhibited α-glucosidase enzyme and their IC50 values were 0.301±0.002 mg/mL and 0.477±0.003 mg/mL, respectively. In addition, EE and ME were determined as noncompetitive inhibitors with inhibitory constant (Ki ) values of 0.48±0.02 mg/mL and 0.46±0.01 mg/mL, respectively. EE in 100 and 300 mg/kg doses caused a significant reduction in formalin-induced edema in mice, demonstrating the anti-inflammatory effect of EE. In DNA protective studies, all of the extracts protected supercoiled plasmid pBR322 DNA against damage caused by Fenton's reagents due to their radical scavenging activities. Our results demonstrated that EE of V. arctostaphylos L. had strong antioxidant, anti-inflammatory, α-glucosidase inhibitory, and DNA protective effects, suggesting that it might be an effective medical plant to prevent or treat diseases associated with oxidative damage and inflammation.

Alzheimer's disease (AD), one of the main causes of dementia, is a neurodegenerative disorder. Cholinesterase inhibitors are used in the treatment of AD, but prolonged use of these drugs can lead to serious side effects. Drug repurposing is an approach that aims to reveal the effectiveness of drugs in different diseases beyond their clinical uses. In this work, we investigated in vitro and in silico inhibitory effects of 11 different drugs on cholinesterases. The results showed that trimebutine, theophylline, and levamisole had the highest acetylcholinesterase inhibitory actions among the tested drugs, and these drugs inhibited by 68.70 ± 0.46, 53.25 ± 3.40, and 44.03 ± 1.20%, respectively at 1000 µM. In addition, these drugs are bound to acetylcholinesterase via competitive manner. Molecular modeling predicted good fitness in acetylcholinesterase active site for these drugs and possible central nervous system action for trimebutine. All of these results demonstrated that trimebutine was determined to be the drug with the highest potential for use in AD.