Bidens pilosa Extract Administered after Symptom Onset Attenuates Glial Activation, Improves Motor Performance, and Prolongs Survival in a Mouse Model of Amyotrophic Lateral Sclerosis
Bidens pilosa Extract Administered after Symptom Onset Attenuates Glial Activation, Improves Motor Performance, and Prolongs Survival in a Mouse Model of Amyotrophic Lateral Sclerosis
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DOI：
10.1155/2020/1020673
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发表时间：
2020-01-29
影响因子：
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通讯作者：
Ito, Yoshihisa
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文献类型：
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作者：
Kosuge, Yasuhiro;Kaneko, Erina;Ito, Yoshihisa
肌萎缩侧索硬化症（ALS）是一种迟发性神经退行性疾病，其特征在于由上下运动神经元死亡导致的进行性瘫痪。ALS目前尚无有效的药物治疗，两种获批药物利鲁唑和依达拉奉对症状的影响有限，仅能略微延长患者的生命。因此，开发有效的治疗策略至关重要。在这项研究中，我们调查了宫古岛鬼针草（MBP）是否可以减轻超氧化物歧化酶-1 G93 A突变转基因小鼠（G93 A小鼠）ALS模型中观察到的神经功能恶化。我们在神经变性症状发作时（15周龄）向G93 A小鼠口服2 g/kg/天MBP，直至死亡。与溶剂处理的ALS模型小鼠相比，MBP处理显著延长ALS模型小鼠的寿命约20天，并显著改善运动表现。MBP治疗阻止了疾病末期（18周龄）G93 A小鼠脊髓中神经元标记蛋白SMI 32表达的减少，并减弱了星形胶质细胞（通过GFAP检测）和小胶质细胞（通过Iba-1检测）的活化。我们的研究结果表明，在ALS症状发作后给予MBP抑制了G93 A ALS模型小鼠脊髓中小胶质细胞和星形胶质细胞的炎症活化，从而改善了它们的生活质量。MBP有可能成为ALS的潜在治疗药物。
Amyotrophic lateral sclerosis (ALS) is a late-onset neurodegenerative disorder characterized by progressive paralysis resulting from the death of upper and lower motor neurons. There is currently no effective pharmacological treatment for ALS, and the two approved drugs riluzole and edaravone have limited effects on the symptoms and only slightly prolong the life of patients. Therefore, the development of effective therapeutic strategies is of paramount importance. In this study, we investigated whether Miyako Island Bidens pilosa (MBP) can alleviate the neurological deterioration observed in a superoxide dismutase-1 G93A mutant transgenic mouse (G93A mouse) model of ALS. We orally administered 2 g/kg/day of MBP to G93A mice at the onset of symptoms of neurodegeneration (15 weeks old) until death. Treatment with MBP markedly prolonged the life of ALS model mice by approximately 20 days compared to that of vehicle-treated ALS model mice and significantly improved motor performance. MBP treatment prevented the reduction in SMI32 expression, a neuronal marker protein, and attenuated astrocyte (detected by GFAP) and microglia (detected by Iba-1) activation in the spinal cord of G93A mice at the end stage of the disease (18 weeks old). Our results indicate that MBP administered after the onset of ALS symptoms suppressed the inflammatory activation of microglia and astrocytes in the spinal cord of the G93A ALS model mice, thus improving their quality of life. MBP may be a potential therapeutic agent for ALS.