Ling-Gui-Zhu-Gan Decoction Alleviates Cognitive Deficits in Alzheimer’s Disease by Activating the Nuclear Factor-Erythroid Factor 2-Related Factor 2/The Antioxidant Responsive Element Signaling Pathway

Alzheimer’s disease is a common neurodegenerative disorder. Ling-Gui-Zhu-Gan decoction has anti-inflammatory, anti-tumor, and immune-regulating effects and is a representative agent for strengthening the spleen and promoting water retention. The present study aimed to investigate the underlying mechanism of Ling-Gui-Zhu-Gan decoction in alleviating Alzheimer’s disease. Alzheimer’s disease in vitro and in vivo models were constructed by exposing SH-SY5Y cells to β-amyloid 1-42 and injecting β-amyloid 1-42 into Sprague-Dawley rats, respectively. The Morris water maze test was used to assess cognitive decline in rats. Cell counting kit-8, flow cytometry analysis, and enzyme-linked immunosorbent assay were conducted to determine cell viability, apoptosis, and inflammation. β-amyloid 1-42 treatment induced SH-SY5Y cell apoptosis, evoked inflammation response and oxidative stress while hindering cell proliferation. Ling-Gui-Zhu-Gan decoction antagonized the effect of β-amyloid 1-42 on SH-SY5Y cells by activating the nuclear factor erythroid 2-related factor 2/antioxidant response element signaling pathway. In addition, Ling-Gui-Zhu-Gan decoction improved memory and learning abilities and alleviated neuropathologic lesions, inflammation response, and neurotoxicity in Alzheimer’s disease rats in a dose-dependent manner by upregulating nuclear factor erythroid 2-related factor 2/antioxidant response element pathway. The Ling-Gui-Zhu-Gan decoction improved the spatial learning and memory ability of Alzheimer’s disease rats by upregulating the nuclear factor erythroid 2-related factor 2/antioxidant response element signaling pathway to counteract the imbalance in the body’s oxidative stress levels and the damage caused by neuroinflammation.