Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Neuroprotective effect of thiamine triethylorthoformate conjugate against Parkinson disease in a mouse model

Yan Dong, Qing Xu, Xi Jia, Chao Li, Dan Xu, Yang Jiao

Department of Neurology, Hong Qi Hospital Affiliated to MuDan Jiang Medical University, MuDan Jiang City, Heil Long Jiang Province-157000, China;

For correspondence:- Yang Jiao Email: SacksMerlehem@yahoo.com Tel:+864536582800

Accepted: 22 April 2019 Published: 31 May 2019

Citation: Dong Y, Xu Q, Jia X, Li C, Xu D, Jiao Y. Neuroprotective effect of thiamine triethylorthoformate conjugate against Parkinson disease in a mouse model. Trop J Pharm Res 2019; 18(5):1041-1047 doi: 10.4314/tjpr.v18i5.18

© 2019 The authors.
This is an Open Access article that uses a funding model which does not charge readers or their institutions for access and distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0) and the Budapest Open Access Initiative (http://www.budapestopenaccessinitiative.org/read), which permit unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited..

Abstract

Purpose: To investigate the effect of thiamine triethylorthoformate conjugate (TTO) on Parkinson disease (PD) in vitro and in vivo in a mice model.

Methods: The effect of TTO on behavioural changes in PD mouse model was studied using pole, traction and swimming tests. Astrocyte proliferation after TTO treatment was assessed using 3 (4, 5 dimethyl 2 thi¬azolyl) 2, 5 diphenyl 2 H tetrazolium bromide (MTT) assay. Apoptosis was determined with flow cytometry using Annexin V Fluorescein isothiocyanate kit.

Results: Treatment of PD mice with TTO led to a decrease in climbing time, increase in suspension score and enhancement of swimming score, when compared to the untreated group (p < 0.05). Treatment of astrocytes with TTO prior to MPP incubation significantly increased proliferation (p < 0.05). Apoptosis induction in astrocytes by MPP was attenuated by pre-treatment with TTO. Pre-treatment of astrocytes with 10 µM TTO markedly reduced JNK activation, when compared to astrocytes incubated with MPP alone (p < 0.05). Up-regulation of Bax and down-regulation of Bcl 2 by MPP in astrocytes were attenuated by pre-treatment with TTO. MPP-induced up-regulation of cleaved caspase 3 was suppressed in astrocytes by TTO pre-treatment (p < 0.05).

Conclusion: Treatment with TTO prevents MPP⁺-induced neuronal damage in vitro in astrocytes and in vivo in mice. The neuro-protective effect of TTO involves down-regulation of JNK activation, inhibition of caspase-3 level, decrease in Bax and increase in Bcl-2 expression. Thus, TTO has a potential for use in the treatment of Parkinson’s disease.

Keywords: Thiamine-triethylorthoformate, Parkinsonâ€™s disease, Neurodegeneration, Inflammation, Inflammation, Oxidative damage