NEUROPROTECTIVE PROPERTY OF YELLOW TURMERIC (CURCUMA LONGA Linn) AND WHITE TURMERIC (CURCUMA ZEDOARIA Rosc) ON MITOCHONDRIAL DYSFUNCTION AND NEUROTRANSMITTER DYSREGULATION IN MANGANESE TOXIFIED RATS

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 viii 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.