Ginkgo biloba affords dose-dependent protection against 6-hydroxydopamine-induced parkinsonism in rats: Neurobehavioural, neurochemical and immunohistochemical evidences

Muzamil Ahmad, Sofiyan Saleem, Abdullah Shafique Ahmad, Seema Yousuf, Mubeen Ahmad Ansari, M. Badruzzaman Khan, Tauheed Ishrat, Rajnish Kumar Chaturvedi, Ashok Kumar Agrawal, Fakhrul Islam

Research output: Contribution to journalArticle

116 Scopus citations

Abstract

Ginkgo biloba extract (EGb), a potent antioxidant and monoamine oxidase B (MAO-B) inhibitor, was evaluated for its anti-parkinsonian effects in a 6-hydroxydopamine (6-OHDA) rat model of the disease. Rats were treated with 50, 100, and 150 mg/kg EGb for 3 weeks. On day 21, 2 μL 6-OHDA (10 μg in 0.1% ascorbic acid saline) was injected into the right striatum, while the sham-operated group received 2 μL of vehicle. Three weeks after 6-OHDA injection, rats were tested for rotational behaviour, locomotor activity, and muscular coordination. After 6 weeks, they were killed to estimate the generation of thiobarbituric acid reactive substances (TBARS) and reduced glutathione (GSH) content, to measure activities of glutathione-S-transferase (GST), glutathione reductase (GR), glutathione peroxidase (GPx), catalase, and superoxide dismutase (SOD), and to quantify catecholamines, dopamine (DA) D2 receptor binding, and tyrosine hydroxylase-immunoreactive (TH-IR) fibre density. 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 EGb. The lesion was followed by an increased generation of TBARS and significant depletion of GSH content in substantia nigra, which was gradually restored with EGb treatment. EGb also dose-dependently restored the activities of glutathione-dependent enzymes, catalase, and SOD in striatum, which had reduced significantly by lesioning. A significant decrease in the level of DA and its metabolites and an increase in the number of dopaminergic D2 receptors in striatum were observed after 6-OHDA injection, both of which were significantly recovered following EGb treatment. Finally, all of these results were exhibited by an increase in the density of TH-IR fibers in the ipsilateral substantia nigra of the lesioned group following treatment with EGb; the lesioning had induced almost a complete loss of TH-IR fibers. Considering our behavioural studies, biochemical analysis, and immunohistochemical observation, we conclude that EGb can be used as a therapeutic approach to check the neuronal loss following parkinsonism.

Original languageEnglish (US)
Pages (from-to)94-104
Number of pages11
JournalJournal of Neurochemistry
Volume93
Issue number1
DOIs
StatePublished - Apr 1 2005
Externally publishedYes

Keywords

  • 6-hydroxydopamine
  • Antioxidant
  • Dopamine
  • Ginkgo biloba
  • Oxidative stress
  • Parkinson's disease
  • Tyrosine hydroxylase

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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