Attenuation by Nardostachys jatamansi of 6-hydroxydopamine-induced parkinsonism in rats: behavioral, neurochemical, and immunohistochemical studies.
Parkinson's disease (PD) is one of the commonest neurodegenerative diseases, and oxidative stress has been evidenced to play a vital role in its causation. In the present study, we evaluated whether ethanolic extract of Nardostachys jatamansi roots (ENj), an antioxidant and enhancer of biogenic amines, can slow the neuronal injury in a 6-OHDA-rat model of Parkinson's. Rats were treated with 200, 400, and 600 mg/kg body weight of ENj for 3 weeks. On day 21, 2 microl of 6-OHDA (12 microg in 0.01% in ascorbic acid-saline) was infused into the right striatum, while the sham-operated group received 2 microl of vehicle. Three weeks after the 6-OHDA injection, the rats were tested for neurobehavioural activity and were sacrificed after 6 weeks for the estimation of lipid peroxidation, reduced glutathione content, the activities of glutathione-S-transferase, glutathione reductase, glutathione peroxidase, superoxide dismutase and catalase, quantification of catecholamines, dopaminergic D2 receptor binding and tyrosine hydroxylase expression. The increase in drug-induced rotations and deficits in locomotor activity and muscular coordination due to 6-OHDA injections were significantly and dose-dependently restored by ENj. Lesioning was followed by an increased lipid peroxidation and significant depletion of reduced glutathione content in the substantia nigra, which was prevented with ENj pretreatment. The activities of glutathione-dependent enzymes, catalase and superoxide dismutase in striatum, which were reduced significantly by lesioning, were dose-dependently restored by ENj. A significant decrease in the level of dopamine and its metabolites and an increase in the number of dopaminergic D2 receptors in striatum were observed after 6-OHDA injection, and both were significantly recovered following ENj treatment. All of these results were exhibited by an increased density of tyrosine hydroxylase immunoreactive (TH-IR) fibers in the ipsilateral striatum of the lesioned rats following treatment with ENj; 6-OHDA injection had induced almost a complete loss of TH-IR fibers. This study indicates that the extract of Jatamansi might be helpful in attenuating Parkinsonism.
Ahmad
Muzamil
M
Neurotoxicology Laboratory, Department of Medical Elementology and Toxicology, Jamia Hamdard (Hamdard University), Hamdard Nagar, New Delhi 110062, India. mahmad7@jhmi.edu
Yousuf
Seema
S
Khan
M Badruzzaman
MB
Hoda
Md Nasrul
MN
Ahmad
Abdullah Shafique
AS
Ansari
Mubeen Ahmad
MA
Ishrat
Tauheed
T
Agrawal
Ashok Kumar
AK
Islam
Fakhrul
F
D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001522:Behavior, Animal / Q000187:drug effects*; D002374:Catalase / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D007150:Immunohistochemistry; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D032404:Nardostachys / Q000737:chemistry*; D016627:Oxidopamine; D010302:Parkinson Disease, Secondary / Q000139:chemically induced* / Q000517:prevention & control* / Q000523:psychology; D018517:Plant Roots / Q000737:chemistry; D011597:Psychomotor Performance / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D017448:Receptors, Dopamine D2 / Q000187:drug effects; D013239:Stereotyped Behavior / Q000187:drug effects; D013482:Superoxide Dismutase / Q000378:metabolism; D013565:Sympatholytics; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D000975:Antioxidants; D017448:Receptors, Dopamine D2; D013565:Sympatholytics; D017392:Thiobarbituric Acid Reactive Substances; D016627:Oxidopamine; D002374:Catalase; D014446:Tyrosine 3-Monooxygenase; D013482:Superoxide Dismutase; D005980:Glutathione Reductase; D005982:Glutathione Transferase; D005978:Glutathione; D004298:Dopamine