Khan_2023_Antioxidants.(Basel)_12_

Feralolide, a dihydroisocoumarin, was isolated from the methanolic extract of resin of Aloe vera. The present study aims to investigate the in vivo ability of feralolide to ameliorate memory impairment induced by scopolamine using a battery of in vitro assays, such as antioxidant and acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibition, and in vivo animal models, including elevated plus maze, Morris water maze, passive avoidance, and novel object recognition tests. Feralolide caused a concentration-dependent inhibition of AChE and BuChE enzymes with IC(50) values of 55 and 52 microg/mL, respectively, and antioxidant activity against 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2, 2'-azinobis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) with IC(50) values 170 and 220 microg/mL, respectively. Feralolide reversed the scopolamine-induced amnesia as indicated by a dose-dependent decrease in escape latency, path length, and passing frequency in the Morris water maze test compared with the relevant control. The compound also significantly increased the discrimination index in a dose-dependent manner in NORT and decreased transfer latency in EPM, reflective of its memory-enhancing effect. Furthermore, feralolide also caused significant dose-dependent elevation in the step-down latency (SDL) in the passive avoidance test. The results indicated that feralolide might be a helpful memory restorative mediator in treating cognitive disorders such as Alzheimer's disease.