title: A Novel Ligustrazine Derivative T-VA Prevents Neurotoxicity in Differentiated PC12 Cells and Protects the Brain against Ischemia Injury in MCAO Rats.
abstract: 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 Ca(2+)-Mg(2+) 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.
authors.forename: Guoliang
authors.initials: G
authors.lastname: Li
authors.affiliation: School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 100102, China. Liguoliangsx@163.com.
authors.forename: Guoling
authors.initials: G
authors.lastname: Li
authors.affiliation: School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 100102, China. tyf0323@126.com.
authors.forename: Yufei
authors.initials: Y
authors.lastname: Tian
authors.affiliation: Department of Pathology, Beijing University of Chinese Medicine, Beijing 100029, China. zyz100102@126.com.
authors.forename: Yuzhong
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 100102, China. limin516@163.com.
authors.forename: Ying
authors.initials: Y
authors.lastname: Hong
authors.affiliation: School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 100102, China. cnhbhyz@hotmail.com.
authors.forename: Yingzhi
authors.initials: Y
authors.lastname: Hao
authors.affiliation: Department of Pathology, Beijing University of Chinese Medicine, Beijing 100029, China. springxiao-85@163.com.
authors.forename: Chunxiao
authors.initials: C
authors.lastname: Chen
authors.affiliation: School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 100102, China. wpl581@126.com.
authors.forename: Penglong
authors.initials: P
authors.lastname: Wang
authors.affiliation: School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 100102, China. hm_lei@126.com.
authors.forename: Haimin
authors.initials: H
authors.lastname: Lei
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D002545:Brain Ischemia / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D017301:Ca(2+) Mg(2+)-ATPase / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D016328:NF-kappa B / Q000378:metabolism; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology*; D016716:PC12 Cells; D011719:Pyrazines / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D020521:Stroke / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D013482:Superoxide Dismutase / Q000378:metabolism; D023382:Toxicity Tests, Acute; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D016328:NF-kappa B; D018696:Neuroprotective Agents; D011719:Pyrazines; D042461:Vascular Endothelial Growth Factor A; D051546:Cyclooxygenase 2; D013482:Superoxide Dismutase; D017301:Ca(2+) Mg(2+)-ATPase; C017953:tetramethylpyrazine
keywords: NF-κB/p65; VEGF; ligustrazine derivative; middle cerebral artery occlusion (MCAO); neuroprotection