Neuroprotective effects of myricetin against rotenone-ınduced parkinsonian neurotoxicity: a multidimensional analysis in rats.

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by dopaminergic neuronal loss, oxidative stress (OS), and α-synuclein pathology. As OS is a major contributor to neuronal injury in PD, therapeutic approaches targeting redox homeostasis have attracted increasing interest. Rotenone (RTN)-induced Parkinsonian-like features closely resemble key aspects of human PD. Myricetin (MYR), a natural flavonol with antioxidant and anti-apoptotic properties, has emerged as a potential neuroprotective agent. This study aimed to evaluate the neuroprotective effects of MYR against RTN-induced neurotoxicity in rats using behavioral, biochemical, and histopathological assessments. Twenty-eight Wistar albino rats (14 males and 14 females) were randomly assigned to control, RTN (3 mg/kg, s.c. for 6 days), and RTN+MYR (5 mg/kg i.p. plus RTN) groups, with equal sex distribution among the experimental groups. Behavioral performance was assessed using rotarod, accelerod, open field, cylinder, hot plate, and tail flick tests by investigators blinded to group allocation. Brain tissues were analyzed for OS markers and histopathological changes in the cerebral cortex, cerebellum, and hippocampus. RTN significantly impaired motor coordination and exploratory behavior, as evidenced by reduced performance in rotarod, accelerod, open field, and cylinder tests. Hot plate latency was prolonged, whereas tail flick responses remained unchanged. RTN markedly increased malondialdehyde (MDA), total oxidant status and oxidative stress index (OSI) levels while reducing antioxidant defenses, including catalase, glutathione peroxidase and glutathione. Histopathological evaluation revealed widespread neuronal degeneration and hemorrhage in the cerebrum, Purkinje cell loss in the cerebellum, and neuronal shrinkage in the hippocampus. MYR co-treatment significantly improved motor performance and attenuated OS, as indicated by reduced MDA levels and OSI values, along with mitigation of neuronal degeneration. MYR attenuated RTN-induced neurotoxicity and was associated with improved behavioral performance, reduced OS, and preservation of neuronal morphology. These findings support the protective potential of MYR against RTN-induced neurotoxicity exhibiting Parkinsonian-like features. Further studies using therapeutic treatment paradigms are required before clinical translation to PD can be considered.