This study was aimed to test the hypotheses that volatile compounds of musk could attenuate nerve injury and identify the bioactive compounds and potential mechanisms of Musk.
Transient middle cerebral artery occlusion (MCAO) model in vivo in Sprague-Dawley rats (SD rats) was used to test this hypothesis. Collecting ingredients of Musk and their related targets were discerned from the Gas chromatography-olfactory mass spectrometry (GC-O-MS) experiment. Then the potential mechanisms and targets of the compounds were searched by network pharmacology techniques. Finally, the pathway was verified by Western Bolt (WB).
First, Musk treatment significantly up-regulated the relative levels of AKT1, PI3KA, and VEGFA in the hippocampus, and improved the sport functions in the post-MCAO ischemic rats in vivo. Next, twenty potential flavor active compounds were recognized by GC-O-MS. A total of 89 key targets including HIF-1, PIK3CA, TNF signaling pathway, and VEGF were identified. AKT1, HIF1A, PIK3CA, and VEGFA were viewed as the most important genes, which were validated by molecular docking simulation.
The Volatile compounds of musk can attenuate nerve injury and improving post-cerebral ischemic exercise functions by HIF1A pathways, and the combined data provide novel insight for Musk volatile compounds developed as new drug for improving reperfusion injury in acute ischemic stroke.
这项研究旨在验证麝香的挥发性化合物可以减轻神经损伤的假设,并确定麝香的生物活性化合物和潜在机制。
使用Sprague-Dawley大鼠(SD大鼠)的瞬时大脑中动脉闭塞(MCAO)体内模型来检验该假设。从气相色谱-嗅觉质谱(GC-O-MS)实验中识别麝香的成分及其相关目标。然后通过网络药理学技术搜索化合物的潜在机制和靶标。最后,该途径经WesternBolt(WB)验证。
首先,麝香处理显著上调AKT1、PI3KA、和海马中的VEGFA,并改善了MCAO后缺血大鼠体内的运动功能。接下来,GC-O-MS识别了20种潜在的风味活性化合物。共有89个关键目标,包括HIF-1,PIK3CA,TNF信号通路,和VEGF被鉴定。AKT1,HIF1A,PIK3CA,VEGFA被认为是最重要的基因,通过分子对接模拟进行了验证。
麝香的挥发性化合物可以通过HIF1A途径减轻神经损伤并改善脑缺血后运动功能,这些数据为麝香挥发性化合物作为改善急性缺血性卒中再灌注损伤的新药开发提供了新的见解。