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

Abstract

This study aimed to investigate the neuroprotective effect of Zingiber officinale methanol extract (MEZO) on copper sulfate-induced nigrostriatal neurodegeneration in mice. A total of 40 mice (n=8 mice/group) were treated orally with distilled water (10 mL kg -1 ; group 1), CuSO 4 (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 CuSO 4 , followed 1 hour later by MEZO and Vitamin C treatment. Locomotor and neuromuscular performance 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. The results revealed that exposure to CuSO 4 treatment elicited significant reduction in locomotor and neuromuscular competence which was improved following the administration of MEZO. Oral exposure to CuSO 4 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 nigrostriatum histological integrity elicited by CuSO 4 lesioning. Herein, this study suggests that MEZO could be used as a pharmacotherapy in the management and treatment of PD pathophysiology elicited following exposure to CuSO 4 intoxication.