Abstract:
Extensive accumulation of manganese (Mn) in the brain causes central nervous system
dysfunction. At the cellular level, mitochondria and neurotransmitters are potential targets
for Mn neurotoxicity which causes a form of Parkinsonism for which there is the need for
a safer and more effective therapy. The present study investigated the neuroprotective
property of ethanol extracts of Curcuma longa and Curcuma zedoaria rhizomes in Mnchallenged
rat brain homogenates (in vitro) and in manganese-toxified male Wistar rats in
vivo. Complex II-III activity was assessed in rat brain homogenates exposed to (1 M and 10
M) Mn with or without treatment with 200 μg/ml of C. longa or C. zedoaria extracts. In the
in vivo experiment, neurobehavioral, biochemical and histopathological assessments were
carried out on rats administered with Mn (100 mg/kg body weight, i.p.) with or without oral
co-treatment with Curcuma longa or Curcuma zedoaria at 200 and 400 mg/kg body weight
for 8 consecutive days. Treatment with Mn reduced complex II-III activity in brain
homogenates was ameliorated by extracts of C. longa (54.5 %, 33.4 % and 25 % at the
cortical, striatal and cortical regions respectively). Exposure of rats to Mn elicited impaired
neurobehavioral performance in the hanging wire and open field tests which were
significantly improved by treatment with C. longa extract (95.6 % and 92.6 %, respectively)
and C. zedoaria extract (62.5 % and 25 %, respectively). Mn-induced disruption of
neurotransmitter metabolism and function as evidenced by significant reduction in cortical,
striatal and hippocampal acetylcholinesterase, tyrosine hydroxylase and dopamine
concentration but not in the hippocampus coupled with increased monoamine oxidase
activities in the cortical, striatal and hippocampal regions of the brain was ablated by the
treatment with the extracts. Additionally, Mn-induced reduction in the activities of
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glutamine synthetase and glutamine dehydrogenase and increase in the activity of
phosphate activated glutaminase in the discrete brain regions indicating altered
glutamatergic neurotransmission, were ameliorated in the extract-treated rats. The
histopathological evaluation of the cortical, striatal and hippocampal region revealed that
C. longa and C. zedoaria extracts reversed the neuronal degeneration, distorted cerebral
histoarchitecture and sparse number of pyramidal cells observed in Mn-toxified rats.
Comparatively, C. longa showed superior activity to C. zedoaria. These results indicated
that Curcuma longa and Curcuma zedoaria are potential neuroprotective agents against
Mn-neurotoxicity and associated pathologies.
