Efeito mnemônico do extrato do fruto da Eugenia uniflora em um modelo de doença de Parkinson em ratos​

Abstract

Parkinson's disease (PD) is a multisystem neurodegenerative disorder that includes motor and non-motor symptoms, characterized mainly by the degeneration of dopaminergic neurons in the substantia nigra pars compacta and the consequent reduction in dopamine levels in the striatum. However, other brain structures and neurotransmission pathways have also been affected. Clinically available therapy consists mainly of controlling the motor alterations of PD, but it has been insufficient to prevent neurodegenerative progression, oxidative stress, mitochondrial dysfunction, and neuroinflammation, and has no neuroprotective action on cognitive impairments, for example. Pitangueira is extensively used and exploited from its leaves to its fruit. Analysis of fruit extracts has revealed its richness in various classes of polyphenols and anthocyanins. The purple variety of its fruit, pitanga, is the rarest, with twice the phenolic content compared to the red variety. In this context, we propose to investigate the neurorestorative potential of the hydroalcoholic extract of the purple fruit of Eugenia uniflora (HAE-BC) against behavioral impairments related to memory in a PD model. To this end, 90-day-old male and female Wistar rats were subjected to intranasal (i.n.) administration of MPTP (1 mg/nostril) or saline solution. After fully recovering, on day 01, the animals were divided into 5 groups: Control; MPTP; HAE-BC 2000; MPTP + HAE-BC 300 mg/kg or 2000 mg/kg, and daily treatment with HAE-BC via gavage for a period of 14 days was started. Throughout this period, the animals underwent behavioral tests to assess memory. On the 15th day, the animals were euthanized and the hippocampus and striatum were dissected. The analyzed data indicated that both sexes showed memory deficits caused by i.n. administration of MPTP, as observed in behavioral tests such as object recognition, Y maze, and social recognition. Treatment with both doses of HAE-BC (300 and 2000 mg/kg) protected against memory impairments induced by MPTP in all tests performed. Our data also demonstrated the modulation of the BDNF/TrKB/p75NTR pathway and apoptosis, as well as the protective effect on dopaminergic neuronal death and α-synuclein levels induced by MPTP, as some of the mechanisms involved in the pharmacological effect of HAE-BC. Therefore, these results demonstrate that HAE-BC has a neuroprotective effect against cognitive decline and suggest a promising potential of the extract in the search for the treatment of PD​.