Background: Mercuric chloride (HgCl2) severely impairs the central nervous system when humans are exposed
Aims: We investigated the neuroprotective efficiency of Ziziphus spina-christi leaf extract (ZSCLE) on HgCl2-mediated
Methods: Twenty-eight rats were distributed equally into four groups: the control, ZSCLE-treated (300 mg/kg), HgCl2-
treated (0.4 mg/kg), and ZSCLE+HgCl2-treated groups. Animals received their treatments for 28 days.
Results: Supplementation with ZSCLE after HgCl2 exposure prevented the deposition of mercury in the cortical slices. It
also lowered malondialdehyde levels and nitrite and nitrate formation, elevated glutathione levels, activated its associatedantioxidant enzymes, glutathione reductase and glutathione peroxidase, and upregulated the transcription of catalase and
superoxide dismutase and their activities were accordingly increased. Moreover, ZSCLE activated the expression of nuclear
factor erythroid 2-related factor 2 and heme oxygenase-1 when compared with the HgCl2 group. Notably, post-treatment
with ZSCLE increased the activity of acetylcholinesterase and ameliorated the histopathological changes associated with
HgCl2 exposure. Furthermore, ZSCLE blocked cortical inflammation, as observed by the lowered mRNA expression and
protein levels of interleukin-1 beta and tumor necrosis factor-alpha, as well as decreased mRNA expression of inducible
nitric oxide synthase. In addition, ZSCLE decreased neuron loss by preventing apoptosis in the cortical tissue upon HgCl2
Conclusion: Based on the obtained findings, we suggest that ZSCLE supplementation could be applied as a neuroprotective
agent to decrease neuron damage following HgCl2 toxicity.