A Novel Ligustrazine Derivative T-VA Prevents Neurotoxicity in Differentiated PC12 Cells and Protects the Brain against Ischemia Injury in MCAO Rats

International Journal of Molecular Sciences

Guoling Li²  Yufei Tian²  Yuzhong Zhang¹  Ying Hong²  Yingzhi Hao²  Chunxiao Chen¹  Penglong Wang²  Haimin Lei² 

[1] Department of Pathology, Beijing University of Chinese Medicine, Beijing 100029, China; E-Mails:;School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 100102, China; E-Mails:

关键词: ligustrazine derivative;    neuroprotection;    NF-κB/p65;    VEGF;    middle cerebral artery occlusion (MCAO);   

DOI  :  10.3390/ijms160921759

来源: mdpi

【 摘 要 】

Broad-spectrum drugs appear to be more promising for the treatment of acute ischemic stroke. In our previous work, a new ligustrazine derivative (3,5,6-trimethylpyrazin-2-yl) methyl 3-methoxy-4-[(3,5,6-trimethylpyrazin-2-yl)methoxy]benzoate (T-VA) showed neuroprotective effect on injured PC12 cells (EC₅₀ = 4.249 µM). In the current study, we show that this beneficial effect was due to the modulation of nuclear transcription factor-κB/p65 (NF-κB/p65) and cyclooxygenase-2 (COX-2) expressions. We also show that T-VA exhibited neuroprotective effect in a rat model of ischemic stroke with concomitant improvement of motor functions. We propose that the protective effect observed in vivo is owing to increased vascular endothelial growth factor (VEGF) expression, decreased oxidative stress, and up-regulation of Ca²⁺–Mg²⁺ ATP enzyme activity. Altogether, our results warrant further studies on the utility of T-VA for the potential treatment of ischemic brain injuries, such as stroke.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.