Department of Neurology and Anesthesiology, Shock Trauma and Anesthesiology Research Center, University of Maryland School of Medicine, Baltimore, MD, USA.
Department of Neurology and Anesthesiology, Shock Trauma and Anesthesiology Research Center, University of Maryland School of Medicine, Baltimore, MD, USA.
Pharmacol Res. 2021 Mar;165:105419. doi: 10.1016/j.phrs.2021.105419. Epub 2021 Jan 12.
The search for novel therapeutic agents for the management of cerebral ischemia/stroke has become an appealing research interest in the recent past. Neuroprotective phytochemicals as novel stroke drug candidates have recently drawn significant interests from stroke scientists due to their strong brain protective effects in animal stroke models. The underlying mechanism of action is likely owing to their anti-inflammatory properties, even though other mechanisms such as anti-oxidation and vasculoprotection have also been proposed. It is generally held that the early proinflammatory responses after stroke can lead to a secondary brain injury, mainly due to the damaging effect exerted by over-activation of brain resident microglial cells and infiltration of circulating monocytes and macrophages. This review focuses on the anti-inflammatory properties of bioactive phytochemicals, including activation and polarization of microglia/macrophages in the post-ischemic brain. The latest studies in animal stroke models demonstrate that this group of bioactive phytochemicals exerts their anti-inflammatory effects via attenuation of brain proinflammatory microglia and macrophages M1 polarization while promoting anti-inflammatory microglial and macrophages M2 polarization. As a result, stroked animals treated with brain protective phytochemicals have significantly fewer brain active M1 microglia and macrophages, smaller brain infarct volume, better functional recovery, and better survival rate. Therefore, this review provides insights into a new category of drug candidates for stroke drug development by employing neuroprotective phytochemicals.
在过去的一段时间里，寻找治疗脑缺血/中风的新型治疗药物已成为一个热门的研究课题。神经保护植物化学物质作为新型的中风药物候选物，由于其在动物中风模型中具有强大的脑保护作用，最近引起了中风科学家的极大兴趣。其作用机制可能是由于它们的抗炎特性，尽管也提出了其他机制，如抗氧化和血管保护。一般认为，中风后早期的促炎反应会导致继发性脑损伤，主要是由于脑固有小胶质细胞过度激活和循环单核细胞和巨噬细胞浸润所产生的破坏性作用。本综述重点介绍了生物活性植物化学物质的抗炎特性，包括缺血后大脑中小胶质细胞/巨噬细胞的激活和极化。动物中风模型的最新研究表明，这组生物活性植物化学物质通过减轻脑内促炎小胶质细胞和巨噬细胞 M1 极化来发挥抗炎作用，同时促进抗炎小胶质细胞和巨噬细胞 M2 极化。因此，用脑保护植物化学物质治疗的中风动物，其大脑中活跃的 M1 小胶质细胞和巨噬细胞数量明显减少，脑梗死体积更小，功能恢复更好，存活率更高。因此，本综述通过使用神经保护植物化学物质为中风药物开发提供了一种新的候选药物类别。
