Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Tanshinone IIA protects against dopaminergic neuron degeneration via regulation of DJ-1 and Nrf2/HO-1 pathways in a rodent model of Parkinsonâ€™s disease

Jingzhou Zhang¹, Yahong Wang², Xingwang Ji³, Zunhua Shu⁴

¹The Center of Preventive Treatment of Disease; ²Department of Liver, Spleen and Stomach Diseases, Affiliated Hospital of Changchun University; ³Department of Emergency, The First Clinical Hospital of Jilin Academy of Traditional Chinese Medicine; ⁴Department of Outpatient, Affiliated Hospital of Changchun University of Traditional Chinese Medicine, Changchun, Jilin 130021, China.

For correspondence:- Zunhua Shu Email: SSophiatsco@yahoo.com Tel:+8615204307345

Accepted: 18 April 2019 Published: 31 May 2019

Citation: Zhang J, Wang Y, Ji X, Shu Z. Tanshinone IIA protects against dopaminergic neuron degeneration via regulation of DJ-1 and Nrf2/HO-1 pathways in a rodent model of Parkinsonâ€™s disease. Trop J Pharm Res 2019; 18(5):1017-1025 doi: 10.4314/tjpr.v18i5.15

© 2019 The authors.
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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 MPTP-induced PD in mice. Thus, tanshinone IIA has a good potential for use as a therapy for PD.

Keywords: Tanshinone IIA, Dopamine, DJ-1, Heme oxygenase 1, Nrf2, Parkinsonâ€™s disease