Inhibitory effects of four naturally occurring compounds from Epicoccum nigrum on acetylcholinesterase activity and nitric oxide production in LPS-activated RAW 264.7 cells

Abstract

Background: The role of nitric oxide in the pathogenesis and progression of neurodegenerative illnesses is becoming prominent over the years and the inhibition of acetylcholinesterase (AChE) is considered as a promising strategy in the management of such diseases. This study aims to assess the inhibitory potential of (1) beauvericin, (2) para-hydroxybenzaldehyde, (3) indole-3-carboxylic acid and (4) quinizarin isolated from endophytic fungi Epicoccum nigrum on acetylcholinesterase activity and on nitric oxide production in LPS-stimulated macrophages.

Methods: The inhibition of acetylcholinesterase activity was determined using Ellman’s colorimetric method. Nitric oxide released from macrophages was determined by measuring the nitrite concentration in culture supernatant using the Griess reagent and the cell viability was determined by MTT assay.

Results: The tested compounds exerted concentration-dependent activity against both AChE and NO production. At the highest dose assessed (20 μg/mL) compounds 1 and 4 produced the smallest amount of NO (0.25 μM and 0.5 μM respectively) and their cell viability varied from 88.49% to 93.04%. Compound 1 exhibited the most potent anti-AChE activity (IC₅₀ = 13.49 μg/mL) which however was lower compare to the reference compound galantamine (IC₅₀ = 8.22 μg/mL), while compound 2 and 3 showed moderate activity.

Conclusions: This study revealed that beauvericin is endowed with a potential against AChE activity and NO production. Taking into account the respective role of NO and AChE in the occurrence and the prevention of neurodegenerative diseases, our findings indicate thatbeauvericincan be considered as a good drug candidate that could be further developed for the prevention of neurodegenerative disorders such as Alzheimer's disease.