Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100193, China.
Key Laboratory of Bioactive Substances and Resource Utilization of Chinese Herbal Medicine, Ministry of Education, Beijing 100193, China.
Molecules. 2018 Sep 19;23(9):2401. doi: 10.3390/molecules23092401.
Ischemic stroke is a clinically common cerebrovascular disease whose main risks include necrosis, apoptosis and cerebral infarction, all caused by cerebral ischemia and reperfusion (I/R). Ischemia and reperfusion-induced injury or apoptosis inhibition in human brain tissue may exert an irreplaceable protective effect on ischemic nerves. This process has particular significance for the treatment of stroke patients. However, the development of neuroprotective drugs remains challenging. Radix Scrophulariae, traditionally considered a valuable medicine, has been discovered to have neuroprotective effects. To explore the neuroprotective effects of an aqueous extract of Radix Scrophulariae (RSAE) on cerebral ischemia/reperfusion and their underlying mechanisms, oxygen-glucose deprivation and reperfusion (OGD/R)-induced PC12 cells were used, and a middle cerebral artery occlusion/reperfusion (MCAO/R) mouse model was established. In vitro results showed that 12.5 μg/mL RSAE markedly improved cell viability; inhibited LDH leakage; increased SOD, GSH-Px and CAT enzyme activity; stabilized the mitochondrial membrane potential; and reduced OGD-induced cell injury and apoptosis. Additionally, in vivo results preliminarily suggested that in MCAO/R model mice, RSAE treatments attenuated infarct volume; reduced brain water content and nitric oxide (NO) and malondialdehyde (MDA) concentrations; inhibited I/R-induced neurological deficits; reduced the levels of lactate dehydrogenase (LDH) leakage release; improved antioxidant capacity by upregulating SOD, GSH-Px and CAT enzyme activity; and reduced neuronal apoptosis, necrosis and loss of neurons. Moreover, it was found that RSAE upregulated the expression of Bcl-2 and downregulated the expression of Bax. In addition, the phosphorylation levels of MAPK signal pathways were elucidated via western blot analysis and immunohistochemical evaluation. In summary, this study investigated the neuroprotective effects and potential mechanisms of RSAE on focal cerebral I/R injury in mice. Radix Scrophulariae has been previously identified as a potential neuroprotective natural plant. Hence, our results may offer insight into discovering new active compounds or drugs for the treatment of ischemic stroke. Many new natural active chemicals in this extract may be discovered by chemical separation and identification and may provide new insights into therapeutic targets in stroke patients.
缺血性脑卒中是一种常见的临床脑血管疾病，其主要风险包括坏死、细胞凋亡和脑梗死，所有这些都是由脑缺血和再灌注（I/R）引起的。缺血和再灌注引起的人脑组织损伤或细胞凋亡抑制可能对缺血性神经发挥不可替代的保护作用。这一过程对中风患者的治疗具有特殊意义。然而，神经保护药物的开发仍然具有挑战性。传统上被认为是一种有价值的药物的地黄已被发现具有神经保护作用。为了探讨地黄水提物（RSAE）对脑缺血/再灌注的神经保护作用及其机制，采用氧葡萄糖剥夺和再灌注（OGD/R）诱导的 PC12 细胞和大脑中动脉闭塞/再灌注（MCAO/R）建立了小鼠模型。体外结果表明，12.5μg/mlRSAE 可显著提高细胞活力；抑制 LDH 漏出；增加 SOD、GSH-Px 和 CAT 酶活性；稳定线粒体膜电位；减轻 OGD 诱导的细胞损伤和凋亡。此外，体内结果初步表明，在 MCAO/R 模型小鼠中，RSAE 处理可减轻梗死体积；降低脑含水量和一氧化氮（NO）和丙二醛（MDA）浓度；抑制 I/R 引起的神经功能缺损；降低乳酸脱氢酶（LDH）漏出释放水平；通过上调 SOD、GSH-Px 和 CAT 酶活性提高抗氧化能力；减少神经元凋亡、坏死和神经元丢失。此外，发现 RSAE 上调了 Bcl-2 的表达，下调了 Bax 的表达。此外，还通过 Western blot 分析和免疫组织化学评价阐明了 MAPK 信号通路的磷酸化水平。综上所述，本研究探讨了 RSAE 对小鼠局灶性脑 I/R 损伤的神经保护作用及其潜在机制。地黄以前被确定为一种有潜力的神经保护天然植物。因此，我们的研究结果可能为发现治疗缺血性中风的新活性化合物或药物提供了思路。通过化学分离和鉴定，该提取物中可能会发现许多新的天然活性化学物质，为中风患者的治疗靶点提供新的思路。
