Qi Fu Yin ameliorates neuroinflammation through inhibiting RAGE and TLR4/NF-KB pathway in AD model rats

The purpose of this study is to investigate the therapeutic effect of Qi Fu Yin (QFY) on Alzheimer's disease (AD) both computationally and experimentally. Network pharmacology analysis and molecular docking were conducted to identify potential targets and signaling pathways involved in QFY treating AD. Streptozotocininduced AD rat model was used to verify important targets and predicted pathways. The components of QFY were identified using liquid chromatography-tandem mass spectrometry. The results indicate that the potential targets of QFY are highly enriched for anti-inflammatory pathways. Molecular docking analysis revealed stable structures formed between QFY's active compounds, including stigmasterol, beta-sitosterol, and isorhamnetin, and the identified targets. In vivo, QFY improved cognitive memory in AD rats and reduced the mRNA expression levels of toll-like receptor 4 (TLR4), the receptor for advanced glycation end products (AGER), and the inflammatory factors interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) in the brains of AD rats. Furthermore, QFY effectively reduced nuclear translocation of nuclear factor-kappa B (NF-KB) and inhibited NF-KB and microglia activation. In conclusion, QFY can ameliorate neuroinflammation in AD model rats, partly via the inhibition of TLR4 and RAGE/NF-KB pathway and microglia activation, thereby enhancing learning and memory in AD model rats.