Institute of Meterial Medica Integration and Transformation for Brain Disorders, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, PR China; School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, PR China.
Institute of Meterial Medica Integration and Transformation for Brain Disorders, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, PR China; School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, PR China.
Exp Gerontol. 2021 Aug;151:111400. doi: 10.1016/j.exger.2021.111400. Epub 2021 May 8.
Shenqi Yizhi Granule (SYG), a modern preparation herbs based on the theory of traditional Chinese medicine, has been proved to be effective against Alzheimer's disease in clinical trials, APP/PS1 mice and 5XFAD transgenic mice. But the underlying mechanism remains ambiguous. Increasing evidence supports the crucial role of astrocyte reactivity in the pathogenesis of Alzheimer's disease (AD). In the present study, we attempt to explore the underlying mechanisms of SYG from astrocyte reactivity in Aβ-induced rat model of Alzheimer's disease. After SYG treatment, the impairment of learning and memory induced by Aβ was significantly improved and the hippocampal neuron damages were alleviated. Additionally, the activity of glutamine synthetase and the concentration of glutamate, which might be involved in the cognitive dysfunctions, were outstandingly reduced. Meanwhile, the astrocyte reactivity was also remarkably inhibited. The expressions of JAK2 and STAT3, key proteins in the JAK2/STAT3 signaling pathway that is tightly associated with reactive astrocytes, were clearly attenuated, too. Collectively, our data demonstrate that SYG might exert protective effects on cognitive impairment induced by amyloid-β oligomers via inhibition of astrocyte reactivity regulated by the JAK2/STAT3 signaling pathway. It may be a potential therapeutic for cognitive dysfunctions in many neurological and psychiatric disorders such as Alzheimer's disease.
参芪益智颗粒（SYG）是一种基于中医理论的现代制剂草药，已在临床试验、APP/PS1 小鼠和 5XFAD 转基因小鼠中被证明对阿尔茨海默病有效。但其潜在机制仍不清楚。越来越多的证据支持星形胶质细胞反应在阿尔茨海默病（AD）发病机制中的关键作用。在本研究中，我们试图从 Aβ 诱导的阿尔茨海默病大鼠模型中的星形胶质细胞反应探讨 SYG 的潜在机制。经 SYG 治疗后，Aβ 引起的学习记忆损伤明显改善，海马神经元损伤减轻。此外，可能参与认知功能障碍的谷氨酰胺合成酶活性和谷氨酸浓度也明显降低。同时，星形胶质细胞反应也明显受到抑制。与反应性星形胶质细胞密切相关的 JAK2/STAT3 信号通路中的关键蛋白 JAK2 和 STAT3 的表达也明显减弱。综上所述，我们的数据表明，SYG 可能通过抑制 JAK2/STAT3 信号通路调节的星形胶质细胞反应，对淀粉样β寡聚体诱导的认知障碍发挥保护作用。它可能是治疗许多神经和精神疾病（如阿尔茨海默病）认知功能障碍的一种潜在治疗方法。
