Neuroprotective potential of Zingiber officinale methanol extract in copper sulfate-induced nigrostriatal neurodegeneration in mice

Abstract

Background: Exposures to transition metals such as copper have been investigated in Parkinson’s disease (PD) patients’ brain with the concentrations higher comparative to the non-diseased. However, the mechanistic approach in PD remains largely unexplored.Objectives This study aims to investigate the Zingiber officinale methanol extract (MEZO) neuroprotective effect in mice striatal and nigral neurons after exposure to copper intoxication. Methods: A total of 40 mice (n = 8 mice/group) were treated orally with distilled water (10 mL kg^-1; group 1), copper sulfate (CuSO₄, 20 mg kg^-1; group 2), MEZO (50 and 100 mg kg^-1; group 3 and 4), and vitamin C (100 mg kg^-1; group 5) repeatedly for 28 days. The mice in group 3 – 5 were pre-treated with CuSO₄, followed 1 hour later by MEZO and Vitamin C treatment. Locomotor and neuromuscular performances were assessed using open field, negative geotaxis and tail suspension test, respectively. After termination, markers of oxidative stress and inflammation, neuronal transmission, and histoarchitectural changes were evaluated in the brain tissues. Results: The exposure to CuSO₄ treatment induced significant reduction in locomotor and neuromuscular competence but was improved following the administration of MEZO. Oral exposure to CuSO₄ increased striatal pro-oxidants (malondialdehyde and nitrite), inflammatory mediators (MPO, TNF-α, and IL-6), and α-synuclein levels; and decreased endogenous antioxidant enzymes (glutathione and catalase), anti-inflammatory cytokine (IL-10), dopamine, acetylcholinesterase (AChE) and brain derived neurotophic factor (BDNF) levels in the striatum. However, the administration of MEZO decreased pro-oxidants, inflammatory mediators, and α-synuclein levels; and increased the endogenous antioxidant enzymes, anti-inflammatory cytokine, dopamine, AChE and BDNF levels in the mice striatum in a dose-related manner. Additionally, the administration of MEZO abated the loss of the nigrostriatal neurons as well as the structural integrity after CuSO₄ lesioning. Conclusion: The study suggests that MEZO could be used as a pharmacotherapy in the management and treatment of PD pathophysiology following exposure to CuSO₄ intoxication.