Yang Chih-Hao, Yen Ting-Lin, Hsu Chia-Yuan, Thomas Philip-Aloysius, Sheu Joen-Rong, Jayakumar Thanasekaran
Department of Pharmacology, Taipei Medical University, Taipei 110, Taiwan.
Division of Cardiology, Department of Internal Medicine, Cathay General Hospital, Taipei 200, Taiwan.
Int J Mol Sci. 2017 Jul 27;18(8):1638. doi: 10.3390/ijms18081638.
A key focus in the field of drug discovery has been motivated by the neuroprotection of natural compounds. Cerebral ischemia is a multifaceted pathological process with a series of mechanisms, and a perspective for the development of neuroprotectants from traditional herbal medicine or natural products is a promising treatment for this disease. Natural compounds with the effects of anti-oxidation, anti-inflammation, anti-apoptosis, and neurofunctional regulation exhibit therapeutic effects on experimental ischemic brain injury. Conferring to the pharmacological mechanisms underlying neuroprotection, a study found that androgapholide, a diterpene lactone compound, exhibits varying degrees of neuroprotective activities in both in vitro and in vivo experimental models of stroke. The neuroprotective mechanisms of andrographolide are suggested as: (I) increasing nuclear factor E2-related factor 2-heme oxygenase (Nrf2-HO-1) expression through p38-mitogen activated protein kinase (MAPK) regulation, (II) inducing cerebral endothelial cells (CEC) apoptosis and caspase-3 activation, (III) down regulating Bax, inducible nitric oxide synthase (iNOS), and (IV) inhibiting hydroxyl radical (OH) formation, and activating transcription factor NF-κB signaling pathways. Recently, several researchers have also been trying to unveil the principal mechanisms involved in the neuroprotective effects of andrographolide. Therefore, this review aims to summarize an overview on the neuroprotective effects of andrographolide and exemplifies the essential mechanisms involved. This paper can provide information that andrographolide drug discovery may be a promising strategy for the development of a novel class of neuroprotective drug.
药物研发领域的一个关键重点是受天然化合物的神经保护作用所驱动。脑缺血是一个具有一系列机制的多方面病理过程，从传统草药或天然产物中开发神经保护剂是治疗这种疾病的一种有前景的方法。具有抗氧化、抗炎、抗凋亡和神经功能调节作用的天然化合物对实验性缺血性脑损伤具有治疗作用。根据神经保护的药理学机制，一项研究发现，穿心莲内酯，一种二萜内酯化合物，在体外和体内中风实验模型中均表现出不同程度的神经保护活性。穿心莲内酯的神经保护机制被认为是：（I）通过p38丝裂原活化蛋白激酶（MAPK）调节增加核因子E2相关因子2-血红素加氧酶（Nrf2-HO-1）的表达，（II）诱导脑内皮细胞（CEC）凋亡和半胱天冬酶-3激活，（III）下调Bax、诱导型一氧化氮合酶（iNOS），以及（IV）抑制羟自由基（OH）的形成，并激活转录因子NF-κB信号通路。最近，几位研究人员也一直在试图揭示穿心莲内酯神经保护作用的主要机制。因此，本综述旨在总结穿心莲内酯神经保护作用的概述，并举例说明其中涉及的基本机制。本文可以提供信息，即穿心莲内酯药物研发可能是开发新型神经保护药物的一种有前景的策略。
