Department of Clinical Research, Korea Institute of Oriental Medicine, 1672 Yuseong-daero, Yuseong-gu, Daejeon, 305-811, Republic of Korea.
Mol Neurobiol. 2019 Apr;56(4):2394-2407. doi: 10.1007/s12035-018-1236-0. Epub 2018 Jul 20.
Amyotrophic lateral sclerosis (ALS) is a motor neuron disease characterized by progressive motor function impairment, dysphagia, and respiratory failure. Owing to the complexity of its pathogenic mechanisms, an effective therapy for ALS is lacking. Herbal medicines with multiple targets have good efficacy and low adverse reactions for the treatment of neurodegenerative diseases. In this study, the effects of Bojungikgi-tang (BJIGT), an herbal medicine with eight component herbs, on muscle and spinal cord function were evaluated in an ALS animal model. Animals were randomly divided into three groups: a non-transgenic group (nTg, n = 24), a hSOD1 transgenic group (Tg, n = 24), and a hSOD1 transgenic group in which 8-week-old mice were orally administered BJIGT (1 mg/g) once daily for 6 weeks (Tg+BJIGT, n = 24). The effects of BJIGT were evaluated using a rotarod test, foot-printing, and survival analyses based on Kaplan-Meier survival curves. To determine the biological mechanism underlying the effects of BJIGT in hSOD1 mice, western blotting, transmission electron microscopy, and Bungarotoxin staining were used. BJIGT improved motor function and extended the survival duration of hSOD1 mice. In addition, BJIGT had protective effects, including anti-oxidative and anti-inflammatory effects, in both the spinal cord and muscle of hSOD1 mice. Our results demonstrated that BJIGT causes muscle atrophy and the denervation of neuromuscular junctions in the gastrocnemius of hSOD1 mice. The components of BJIGT may alleviate the symptoms of ALS via different mechanisms, and accordingly, BJIGT treatment may be an effective therapeutic approach.
肌萎缩侧索硬化症（ALS）是一种运动神经元疾病，其特征是进行性运动功能障碍、吞咽困难和呼吸衰竭。由于其发病机制复杂，缺乏有效的 ALS 治疗方法。具有多靶点的草药对治疗神经退行性疾病具有良好的疗效和低不良反应。在这项研究中，评估了八种成分草药组成的草药方剂补阳还五汤（BJIGT）对 ALS 动物模型中肌肉和脊髓功能的影响。动物随机分为三组：非转基因组（nTg，n=24）、hSOD1 转基因组（Tg，n=24）和 hSOD1 转基因组，其中 8 周龄小鼠每日口服 BJIGT（1mg/g）一次，持续 6 周（Tg+BJIGT，n=24）。通过转棒试验、足迹试验和基于 Kaplan-Meier 生存曲线的生存分析评估 BJIGT 的作用。为了确定 BJIGT 在 hSOD1 小鼠中的作用的生物学机制，使用 Western blot、透射电子显微镜和 Bungarotoxin 染色。BJIGT 改善了运动功能，延长了 hSOD1 小鼠的生存时间。此外，BJIGT 在 hSOD1 小鼠的脊髓和肌肉中均具有抗氧化和抗炎作用等保护作用。我们的结果表明，BJIGT 导致 hSOD1 小鼠的肌肉萎缩和运动终板失神经支配。BJIGT 的成分可能通过不同的机制缓解 ALS 的症状，因此，BJIGT 治疗可能是一种有效的治疗方法。
