Sugimoto Kazuo, Liu Jia, Li MingXuan, Song YueBo, Zhang Chi, Zhai ZhiGuang, Gao Ying
Department of Neurology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China.
Institute for Brain Disorders, Beijing University of Chinese Medicine, Beijing, China.
Front Pharmacol. 2021 Oct 19;12:701886. doi: 10.3389/fphar.2021.701886. eCollection 2021.
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease, in the pathogenesis of which oxidative stress (OS) was believed to play a key role. Shenqi Fuzheng Injection (SFI) concocted from two kinds of Chinese medicinal herbs, Radix Codonopsis and Radix Astragali, was proven to be eligible to reduce the OS injury and increase the activity of the nuclear factor-erythroid-2-related factor 2 (Nrf2) pathway, an antioxidant enzymes inducer. We aim to investigate the effects and potential mechanisms underlying the action of SFI on a well-established transgenic mouse model of ALS. Transgenic SOD1-G93A mice were intraperitoneally injected with SFI (40 ml/kg) three times a week from 87 days of age. Motor function, survival, pathological manifestations in the brain, and Nrf2 pathway-related assessments of the mice were performed. SFI treatment efficiently postponed the disease onset ( = 0.022) and extended the overall survival ( = 0.038) of the SOD1-G93A mice. Moreover, SFI significantly reduced motor neuron loss ( < 0.001) and astrocytic activation ( < 0.05) in the motor cortex of the brain of SOD1-G93A mice at 130 days of age. The protective effects of SFI in the SOD1-G93A mice were associated with decreasing the level of malondialdehyde ( < 0.05) and increasing the levels of superoxide dismutase ( < 0.05), Nrf2 ( < 0.05), heme oxygenase-1 ( < 0.05), and glutathione S-transferase ( < 0.05) in the SOD1-G93A mice. The SFI treatment efficiently extended the overall survival and improved the pathological manifestations of the brain alleviating the OS injury and activating the Nrf2 pathway in the animal model of ALS, which made SFI a potentially promising candidate for ALS treatment.
肌萎缩侧索硬化症(ALS)是一种进行性神经退行性疾病,氧化应激(OS)被认为在其发病机制中起关键作用。由党参和黄芪两种中药材制成的参芪扶正注射液(SFI)被证明有资格减轻OS损伤并增加核因子红细胞2相关因子2(Nrf2)途径的活性,Nrf2是一种抗氧化酶诱导剂。我们旨在研究SFI对成熟的ALS转基因小鼠模型作用的效果及潜在机制。从87日龄开始,每周三次给转基因SOD1-G93A小鼠腹腔注射SFI(40毫升/千克)。对小鼠进行运动功能、生存情况、脑部病理表现以及Nrf2途径相关评估。SFI治疗有效推迟了SOD1-G93A小鼠的疾病发作(P = 0.022)并延长了总体生存期(P = 0.038)。此外,SFI显著减少了130日龄SOD1-G93A小鼠大脑运动皮层中的运动神经元损失(P < 0.001)和星形胶质细胞活化(P < 0.05)。SFI对SOD1-G93A小鼠的保护作用与降低丙二醛水平(P < 0.05)以及增加超氧化物歧化酶(P < 0.05)、Nrf2(P < 0.05)、血红素加氧酶-1(P < 0.05)和谷胱甘肽S-转移酶(P < 0.05)水平有关。SFI治疗有效延长了总体生存期并改善了脑部病理表现,减轻了ALS动物模型中的OS损伤并激活了Nrf2途径,这使SFI成为ALS治疗的一个潜在有前景的候选药物。