Análogo do resveratrol, inibidor da acetilcolinesterase in vitro, suprime o déficit cognitivo induzido pela escopolamia em camundongos.

Abstract

The increase of the global population life expectancy is a current phenomenon. According to some researchers, age is the main risk factor that contributes to a higher incidence of the major pathologies over the elderly group, including Alzheimer's disease (AD). AD is estimated to affect over 35 million people globally at a billion-dollar cost for the health systems. Despite the social and economic impact, few pharmacological strategies are available for the management of this progressive and cureless disease. Resveratrol (RSV), a phytoalexin, is known as having several biological properties, including neuroprotection. However, its low bioavailability is still a limiting factor to the clinical use of this phytochemical. A number of RSV analogs have previously been synthesized and tested for their biological actions. RSVA6 has been shown both in silico and in vitro to be able to interact and inhibit the acetylcholinesterase enzyme. In this present study, the antioxidant capacity of RSVA6 was evaluated by the 1,1-diphenyl-2-picrylhydrazine method. Comparing to RSV, the analogue showed inferior action. In vivo assays were conducted in order to test the neuroprotective ability of RSVA6 on scopolamine-induced cognitive impairments. Mice were pretreated with a single dose of RSVA6 (100 mg kg-1; orally) or rivastigmine (1 mg kg-1; intraperitoneally), followed by a 60 min interval before receiving scopolamine (1 mg kg-1) intraperitoneally. RSVA6 prevented cognitive decline in the buried pellet, object recognition and object location tasks. In addition, the derivative had no behavioral effect on the open field and elevated plus maze tests, suggesting no interference on the motor activity and anxious-type behavior. Taken together, the results indicate neuroprotective effect of RSVA6 on scopolamine- induced cognitive dysfunction and suggest the molecule as a potential candidate for the treatment of neurodegenerative diseases, including AD.