Wang Sheue-Er, Lin Ching-Lung, Hsu Chih-Hsiang, Sheu Shuenn-Jyi, Chien Chiang-Ting, Wu Chung-Hsin
Department of Life Science, National Taiwan Normal University, Taipei, Taiwan.
Brion Research Institute of Taiwan, Taipei, Taiwan.
Drug Des Devel Ther. 2015 Feb 16;9:887-900. doi: 10.2147/DDDT.S78015. eCollection 2015.
Huntington's disease (HD) is a neurodegenerative disease characterized by motor dysfunction and early death. Despite years of research, the mechanisms responsible for chronic neurodegeneration of HD remain elusive. Chinese traditional medicines might provide new insights or new therapy for HD. The Chinese herbal formula B401 is a well-known Taiwan-US patent formula and a health supplement for promoting blood circulation and enhancing brain function. This study aimed to elucidate the neuroprotective effects of the Chinese herbal formula B401 on the syndrome of HD. Then, we compared the life span and body weight of R6/2 HD mice with and without oral B401 treatment. The ameliorative effects of B401 on the symptom of HD mice were investigated through behavior tests. Expressions of proteins for neuroprotection, angiogenesis, and inflammation in the brain tissue of R6/2 HD mice were compared by using immunostaining and Western blotting techniques. Our study in vitro showed that viabilities of glutamate-treated SH-SY5Y cells were significantly increased under B401 treatment. Our results in vivo showed that duration of survival was increased, body weight loss was reduced, and motor ability was improved in R6/2 HD mice under oral B401 treatment. Subcutaneous microcirculation was enhanced in 3-month R6/2 HD mice under intraperitoneal B401 injections as observed by using moorFLPI laser Doppler imager. Atrophy of cerebrum, midbrain, and cerebellum in 3-month R6/2 HD mice under oral B401 treatment was alleviated as observed by utilizing magnetic resonance imaging. Evidence from immunostaining and Western blotting analysis showed that expressions of mutant huntingtin and tumor necrosis factor-alpha were reduced, while expressions of brain-derived neurotrophic factor and vascular endothelial growth factor were enhanced in the brain tissue of 2-month R6/2 HD mice under oral B401 treatment. We suggest that the herbal formula B401 can be developed as a medical supplement for ameliorating neurodegenerative diseases of HD via reducing mutant huntingtin aggregation and excitotoxicity, enhancing neuroprotection and angiogenesis, and alleviating inflammation in the brain.
亨廷顿舞蹈症（HD）是一种以运动功能障碍和过早死亡为特征的神经退行性疾病。尽管经过多年研究，HD慢性神经退行性变的机制仍不清楚。中药可能为HD提供新的见解或新的治疗方法。中药配方B401是一项著名的台美专利配方，是一种促进血液循环和增强脑功能的健康补充剂。本研究旨在阐明中药配方B401对HD综合征的神经保护作用。然后，我们比较了口服B401治疗和未治疗的R6/2 HD小鼠的寿命和体重。通过行为测试研究B401对HD小鼠症状的改善作用。使用免疫染色和蛋白质印迹技术比较R6/2 HD小鼠脑组织中神经保护、血管生成和炎症相关蛋白的表达。我们的体外研究表明，在B401治疗下，谷氨酸处理的SH-SY5Y细胞活力显著增加。我们的体内研究结果表明，口服B401治疗的R6/2 HD小鼠存活时间延长，体重减轻减少，运动能力提高。使用moorFLPI激光多普勒成像仪观察到，腹腔注射B401后，3个月大的R6/2 HD小鼠皮下微循环增强。利用磁共振成像观察到，口服B401治疗的3个月大的R6/2 HD小鼠大脑、中脑和小脑的萎缩得到缓解。免疫染色和蛋白质印迹分析的证据表明，口服B401治疗的2个月大的R6/2 HD小鼠脑组织中突变型亨廷顿蛋白和肿瘤坏死因子-α的表达降低，而脑源性神经营养因子和血管内皮生长因子的表达增强。我们建议，中药配方B401可开发为一种医疗补充剂，通过减少突变型亨廷顿蛋白聚集和兴奋性毒性、增强神经保护和血管生成以及减轻脑部炎症来改善HD神经退行性疾病。
