Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Azadiradione exerts anti-inflammatory and anti-oxidant effects, alleviates dopaminergic neurodegeneration and reduces ^5;-synuclein levels in MPTP-induced mouse model of Parkinson disease

Tao Jin¹, Xuemei Cao², Zongwen Gao², Xue-Qin Yan³

¹Department of Pharmacy, Jinan Central Hospital, Jinan, Shandong 250013; ²Department of Pharmacy, Binzhou Central Hospital, Binzhou, Shandong 251700; ³Department of Neurology, The Second Peopleâ€™s Hospital of Jingmen, Jingmen, Hubei 448000, China.

For correspondence:- Xue-Qin Yan Email: 382910396@qq.com Tel:+867246812526

Accepted: 21 October 2019 Published: 30 November 2019

Citation: Jin T, Cao X, Gao Z, Yan X. Azadiradione exerts anti-inflammatory and anti-oxidant effects, alleviates dopaminergic neurodegeneration and reduces ^5;-synuclein levels in MPTP-induced mouse model of Parkinson disease. Trop J Pharm Res 2019; 18(11):2331-2340 doi: 10.4314/tjpr.v18i11.15

© 2019 The authors.
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Abstract

Purpose: To determine the effects of azadiradione (AZD), a tetracyclic triterpenoid, in 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)–induced experimental rodent model of Parkinson’s disease (PD).

Methods: C57BL/6 mice were intraperitoneally injected MPTP at a dose of 20 mg/kg body weight in saline (4 times at 2-h intervals). Azadiradione (AZD) at doses of 12.5, 25 or 50 mg/kg were administered to separate groups of mice via oral gavage for 6 days prior to MPTP injection.

Results: Azadiradione (AZD) reduced loss of tyrosine hydroxylase (TH)-positive neurons. TH-positive counts increased to 91.44 % on treatment with 50 mg/kg AZD. Significantly (p < 0.05) down-regulated α-synuclein levels were seen following MPTP induction and AZD administration. expressions of Bax, Bcl-2 and cleaved-caspase-3 were significantly downregulated (p < 0.05). Treatment with AZD inhibited the translocation of Cyt-C to the mitochondria, thereby preventing activation of apoptotic cascade. Oxidative stress induced by MPTP was significantly reduced by AZD via up-regulation of glutathione levels and SOD1/HO-1 expression. Azadiradione, at a dose of 50 mg/kg, significantly (p < 0.05) reduced ROS levels from 210.6 19.23%, and also reduced the levels of inflammatory cytokines.

Conclusion: These results indicate the anti-inflammatory, anti-oxidative and neuroprotective properties of AZD in mice. Thus, AZD is a potential candidate drug for the management of PD. However, further studies are required to ascertain this.

Keywords: Azadiradione, Alpha-synuclein dopamine, 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP), Neurodegeneration, Parkinson disease