Hochu-Ekki-To Improves Motor Function in an Amyotrophic Lateral Sclerosis Animal Model
Hochu-Ekki-To Improves Motor Function in an Amyotrophic Lateral Sclerosis Animal Model
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DOI：
10.3390/nu11112644
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发表时间：
2019-11-01
期刊：
影响因子：
5.9
通讯作者：
Yang, Eun Jin
中科院分区：
文献类型：
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作者：
Cai, Mudan;Yang, Eun Jin
Hochu-ekki-to（韩国的Bojungikgi-Tang (BJIGT)；中国的Bu-Zhong-Yi-Qi-Tang）是一种传统草药处方，已在亚洲广泛使用。 Hochu-ekki-to (HET) 用于增强呼吸系统疾病的免疫系统，改善与慢性疾病相关的营养状况，增强粘膜免疫系统，并改善学习和记忆。肌萎缩侧索硬化症（ALS）的病理特征是运动神经元细胞死亡和肌肉麻痹，是一种成人发病的运动神经元疾病。使用 ALS 模型的临床和体外/体内研究已经报道了 ALS 的几种病理机制。然而，潜在的机制仍然难以捉摸，在为 ALS 患者开发有效药物之前，需要确定关键的病理靶点。由于ALS是一种涉及运动神经元死亡和骨骼肌麻痹的疾病，因此具有最佳治疗效果的合适疗法将涉及运动神经元靶标与骨骼肌靶标相结合。草药对复杂疾病有效，因为它由针对多个目标的多种成分组成。因此，我们研究了草药 HET 对 hSOD1(G93A) 转基因小鼠运动功能和生存的影响。 hSOD1(G93A)转基因小鼠从2月龄(症状前阶段)起每天口服一次HET，持续6周。我们使用旋转杆测试和足印测试来检查运动活动，并使用蛋白质印迹和 H&E 染色来评估 HET 对小鼠腓肠肌和腰椎 (L4-5) 脊髓的影响。我们发现 HET 治疗显着抑制 hSOD1（G93A）转基因小鼠的脊髓和腓肠肌的炎症和氧化应激。此外，HET 治疗改善了 hSOD1（G93A）转基因小鼠的运动功能并延长了生存期。我们的研究结果表明，HET 治疗可能会调节肌肉和神经元的免疫反应，从而延缓 ALS 模型的疾病进展。
Hochu-ekki-to (Bojungikgi-Tang (BJIGT) in Korea; Bu-Zhong-Yi-Qi Tang in Chinese), a traditional herbal prescription, has been widely used in Asia. Hochu-ekki-to (HET) is used to enhance the immune system in respiratory disorders, improve the nutritional status associated with chronic diseases, enhance the mucosal immune system, and improve learning and memory. Amyotrophic lateral sclerosis (ALS) is pathologically characterized by motor neuron cell death and muscle paralysis, and is an adult-onset motor neuron disease. Several pathological mechanisms of ALS have been reported by clinical and in vitro/in vivo studies using ALS models. However, the underlying mechanisms remain elusive, and the critical pathological target needs to be identified before effective drugs can be developed for patients with ALS. Since ALS is a disease involving both motor neuron death and skeletal muscle paralysis, suitable therapy with optimal treatment effects would involve a motor neuron target combined with a skeletal muscle target. Herbal medicine is effective for complex diseases because it consists of multiple components for multiple targets. Therefore, we investigated the effect of the herbal medicine HET on motor function and survival in hSOD1(G93A) transgenic mice. HET was orally administered once a day for 6 weeks from the age of 2 months (the pre-symptomatic stage) of hSOD1(G93A) transgenic mice. We used the rota-rod test and foot printing test to examine motor activity, and Western blotting and H&E staining for evaluation of the effects of HET in the gastrocnemius muscle and lumbar (L4-5) spinal cord of mice. We found that HET treatment dramatically inhibited inflammation and oxidative stress both in the spinal cord and gastrocnemius of hSOD1(G93A) transgenic mice. Furthermore, HET treatment improved motor function and extended the survival of hSOD1(G93A) transgenic mice. Our findings suggest that HET treatment may modulate the immune reaction in muscles and neurons to delay disease progression in a model of ALS.