Park Hyunjun, Kang Shinwoo, Nam Eunjoo, Suh Yoo-Hun, Chang Keun-A
Department of Health Sciences and Technology, Gachon Advanced Institute for Health Sciences and Technology (GAIHST), Gachon University, Incheon, South Korea.
Neuroscience Research Institute, Gachon University, Incheon, South Korea.
Front Pharmacol. 2019 Jan 24;10:2. doi: 10.3389/fphar.2019.00002. eCollection 2019.
Willdenow is a herb known for its therapeutic effects in insomnia, depression, disorientation, and memory impairment. In Alzheimer's disease (AD) animal model, there has been no report on the effects of memory and cognitive impairment. PSM-04, an extract from the root of Willdenow, was developed with improved bioabsorption. The present study aimed to investigate the neuroprotective effects of PSM-04 on AD and reveal the possible molecular mechanism. The neuroprotective effect of PSM-04 in primary cortical neurons treated with L-glutamate, oligomeric Aβ, or HO. PSM-04 exhibited significant neuroprotective effects against neurotoxicity induced by L-glutamate or oligomeric Aβ was studied. PSM-04 exhibited significant neuroprotective effects against neurotoxicity induced by L-glutamate or oligomeric Aβ. Oxidative stress induced by ROS was monitored using the DCF-DA assay, and apoptosis was assessed using the TUNEL assay in primary cortical neurons treated with HO or oligomeric Aβ. PSM-04 also decreased oxidative stress induced by HO and apoptotic cell death induced by oligomeric Aβ. We evaluated the therapeutic effect of PSM-04 in 5xFAD (Tg) mice, an animal model for AD. PSM-04 was orally administered to 4-month-old 5xFAD mice for 2 months. To confirm the degree of cognitive impairment, a novel object recognition task was performed. The treatment with PSM-04 significantly alleviated cognitive impairments in Tg mice. In addition, amyloid plaques and gliosis decreased significantly in the brains of PSM-04-administered Tg mice compared with Tg-vehicle mice. Furthermore, the administration of PSM-04 increased the superoxide dismutase-2 (SOD-2) protein level in hippocampal brain tissues. Our results indicated that PSM-04 showed therapeutic effects by alleviating cognitive impairment and decreasing amyloid plaque deposition in Tg mice. Therefore, PSM-04 was considered as a potential pharmacological agent for neuroprotective effects in neurodegenerative diseases, including AD.
威尔登诺草是一种以对失眠、抑郁、定向障碍和记忆障碍具有治疗作用而闻名的草药。在阿尔茨海默病（AD）动物模型中，尚未有关于其对记忆和认知障碍影响的报道。PSM - 04是从威尔登诺草根部提取的一种提取物，其生物吸收性得到了改善。本研究旨在探讨PSM - 04对AD的神经保护作用，并揭示其可能的分子机制。研究了PSM - 04在经L - 谷氨酸、寡聚Aβ或HO处理的原代皮质神经元中的神经保护作用。PSM - 04对L - 谷氨酸或寡聚Aβ诱导的神经毒性表现出显著的神经保护作用。使用DCF - DA检测法监测ROS诱导的氧化应激，并在经HO或寡聚Aβ处理的原代皮质神经元中使用TUNEL检测法评估细胞凋亡。PSM - 04还降低了HO诱导的氧化应激和寡聚Aβ诱导的凋亡细胞死亡。我们评估了PSM - 04在5xFAD（Tg）小鼠（一种AD动物模型）中的治疗效果。将PSM - 04口服给予4个月大的5xFAD小鼠，持续2个月。为了确认认知障碍的程度，进行了一项新物体识别任务。PSM - 04治疗显著减轻了Tg小鼠的认知障碍。此外，与Tg - 载体小鼠相比，给予PSM - 04的Tg小鼠大脑中的淀粉样斑块和胶质增生显著减少。此外，给予PSM - 04提高了海马脑组织中超氧化物歧化酶 - 2（SOD - 2）蛋白水平。我们的结果表明，PSM - 04通过减轻Tg小鼠的认知障碍和减少淀粉样斑块沉积显示出治疗效果。因此，PSM - 04被认为是一种在包括AD在内的神经退行性疾病中具有神经保护作用的潜在药物制剂。
