Shenqi Yizhi Granule attenuates Aβ1–42 induced cognitive dysfunction via inhibiting JAK2/STAT3 activated astrocyte reactivity

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 Aβ1–42-induced rat model of Alzheimer's disease. After SYG treatment, the impairment of learning and memory induced by Aβ1–42 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.