Department of Pharmacology, PSG College of Pharmacy, Peelamedu, Coimbatore, Tamil Nadu, 641004, India.
Department of Medicinal and Biological Chemistry, Frederic and Mary Wolfe Center 292A, University of Toledo, 3000 Arlington Avenue, Toledo, OH, 43614, USA.
Neurochem Res. 2019 May;44(5):1228-1242. doi: 10.1007/s11064-019-02768-7. Epub 2019 Mar 12.
The present study has been aimed to explore the different secondary messengers of the inflammatory pathway NF-κB, kinases (JNK, P38MAPK, GSK3β/βcatenin), apoptosis pathway (Caspase-3 and AIF), and neuronal survival pathway (BDNF) in order to understand the neuroprotective mechanism of aqueous extract of Tribulus terrestris (AQTT). In primary cortical neurons, the ischemic condition was induced through oxygen-glucose deprivation (OGD). Anti-inflammatory activity of AQTT was evaluated in formalin induced inflammation model and carrageenan-induced paw edema test. The bilateral common carotid artery occlusion model was employed for whole animal studies. Treatment of AQTT (100 mg/kg) significantly reduced the inflammation induced by formalin and carrageenan. The neuroprotective mechanism of AQTT (50 and 100 mg/kg) was assessed by pre- and post-administration. The results indicate down regulation of kinases and NFkB, suggesting possible anti-inflammatory activity of AQTT. Additionally, AQTT down regulated both caspase dependent and independent apoptotic pathways suggesting its possible anti-apoptotic activity. The treatment of AQTT also reduced GSK3β levels and increased p-Ser9 GSK3β levels; stabilizing the unphosphorylated form of β-catenin and its translocation into the nucleus suggesting role of AQTT in neuronal survival and GSK3β mediated anti-inflammatory property. In comparison to pretreatment, post treatment of AQTT had lesser effects indicating tribulusterine standardized AQTT may have prophylactic effect. This study can be concluded with the thesis that AQTT has neuroprotective effect through alternating neuroinflammation, apoptosis, and promoting neuron survival. Being that it produced better effect with pretreatment, exploring this with thrombolytic drugs will be beneficial. For the first time AQTT has been reported for this indication.
本研究旨在探讨炎症通路 NF-κB 的不同第二信使、激酶（JNK、P38MAPK、GSK3β/β-catenin）、凋亡通路（Caspase-3 和 AIF）和神经元存活通路（BDNF），以了解蒺藜水提物（AQTT）的神经保护机制。在原代皮质神经元中，通过氧葡萄糖剥夺（OGD）诱导缺血状态。通过甲醛诱导的炎症模型和角叉菜胶诱导的爪肿胀试验评估 AQTT 的抗炎活性。采用双侧颈总动脉闭塞模型进行整体动物研究。AQTT（100mg/kg）治疗可显著减轻甲醛和角叉菜胶诱导的炎症。通过预先和后给药评估 AQTT（50 和 100mg/kg）的神经保护机制。结果表明，激酶和 NFkB 的下调表明 AQTT 可能具有抗炎活性。此外，AQTT 下调了依赖和不依赖半胱天冬酶的凋亡途径，表明其可能具有抗凋亡活性。AQTT 的治疗还降低了 GSK3β 水平并增加了 p-Ser9 GSK3β 水平；稳定了未磷酸化形式的β-catenin 及其向核内易位，表明 AQTT 在神经元存活和 GSK3β 介导的抗炎特性中的作用。与预处理相比，AQTT 的后处理效果较小，表明 tribulusterine 标准化 AQTT 可能具有预防作用。这项研究可以得出结论，AQTT 通过改变神经炎症、凋亡和促进神经元存活来发挥神经保护作用。由于它在预处理中产生了更好的效果，因此与溶栓药物一起探索这一点将是有益的。这是首次报道 AQTT 具有这种适应症。
