Abstract

Purpose: To study the potential neuroprotective effects of tanshinone IIA, a diterpene quinone, in an experimental model of 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-induced Parkinson disease (PD).
 Methods: Mice (C57BL/6) were administered freshly-prepared MPTP at a dose of 20 mg/kg body weight intraperitoneally, 4 times at 2-h intervals, to induce PD. Doses of 12.5, 25 and 50 mg/kg tanshinone IIA were administered to the mice as treatments for PD. Pole and Rota-rod tests were carried out to assess muscular coordination and bradykinesia. Protein expressions, reactive oxygen species (ROS) and malonaldehyde and other parameters were evaluated.
 Results: Tanshinone IIA at doses of 12.5, 25 and 50 mg/kg reduced deficits in muscular coordination and improved learning ability of MPTP-treated mice. It also reduced loss of tyrosine hydroxylase (TH)- positive neurons following MPTP-induction. Tanshinone IIA regulated apoptotic pathway proteins, i.e., Bax and Bcl-2, and inhibited the translocation of Cyt C to the mitochondria. Oxidative stress induced by MPTP was significantly inhibited by tanshinone IIA via up-regulation of DJ-1/Nrf2 /HO-1 expression and reduction of ROS and MDA levels. Brain tissue total glutathione content was increased by tanshinone IIA treatment.
 Conclusion: Tanshinone IIA effectively improves antioxidant status and reduces neuronal loss following MPTP treatment. These results indicate that tanshinone IIA exerts protective effects in MPTPinduced PD in mice. Thus, tanshinone IIA has a good potential for use as a therapy for PD.

Highlights

  • Parkinson’s disease (PD) is a chronic progressive neurodegenerative disorder characterized by postural instability, tremors, muscular stiffness and bradykinesia [1]

  • Tanshinone IIA improved the behaviour of PD mice

  • The effect of tanshinone IIA on MPTP-induced impairment of muscular coordination and bradykinesia was assessed by pole test and Rota-rod test

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Summary

INTRODUCTION

Parkinson’s disease (PD) is a chronic progressive neurodegenerative disorder characterized by postural instability, tremors, muscular stiffness and bradykinesia [1]. Nuclear factor erythroid 2-related factor (Nrf2) regulates the stress-inducible enzyme heme oxygenase 1 (HO-1) [9]. It regulates the expression of nicotinamide adenine dinucleotide phosphate (NADP)H quinone oxidoreductase-1 (NQO1), an antioxidant enzyme which detoxifies protein-bound quinone, and aids in maintenance of reduced forms of α -tocopherol and coenzyme Q10. The mice were held under standard in-house conditions of 12-h day /12-h night cycle, temperature between 22 - 24 °C, and relative humidity of 55 ± 10 %. They were permitted unrestricted access to animal feed and water. Values of p < 0.05 were considered statistically significant

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