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Oxidative Medicine and Cellular Longevity
Volume 2017 (2017), Article ID 7191856, 15 pages
https://doi.org/10.1155/2017/7191856
Research Article

Therapeutic Potential of Novel Twin Compounds Containing Tetramethylpyrazine and Carnitine Substructures in Experimental Ischemic Stroke

1Department of Pharmacology, School of Basic Medical Science, Shandong University, Jinan 250012, China
2Key Laboratory of Neuroprotective Drug Discovery of Shandong Province, Jinan 250012, China

Correspondence should be addressed to Fan Yi; nc.ude.uds@iynaf

Received 8 April 2017; Revised 16 July 2017; Accepted 13 August 2017; Published 13 December 2017

Academic Editor: Perla D. Maldonado

Copyright © 2017 Ziying Wang et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Although studies have seen dramatic advances in the understanding of the pathogenesis of stroke such as oxidative stress, inflammation, excitotoxicity, calcium overload and apoptosis, the delivery of stroke therapies is still a great challenge. In this study, we designed and synthesized a series of novel twin compounds containing tetramethylpyrazine and carnitine substructures and explored their therapeutic potential and mechanism in stroke-related neuronal injury. We first screened the neuroprotective effects of candidate compounds and found that among the tested compounds, LR134 and LR143 exhibited significant neuroprotection as evidenced by reducing cerebral infarct and edema, improving neurological function as well as blood-brain barrier integrity in rats after cerebral ischemia/reperfusion injury. We further demonstrated that the neuroprotective effects of compounds LR134 and LR143 were associated with the reduced inflammatory responses and NADPH oxidase- (NOX2-) mediated oxidative stress and the protection of mitochondria accompanied by the improvement of energy supply. In summary, this study provides direct evidence showing that the novel twin compounds containing tetramethylpyrazine and carnitine substructures have neuroprotective effects with multiple therapeutic targets, suggesting that modulation of these chemical structures may be an innovative therapeutic strategy for treating patients with stroke.