Mechanistic Study of Huangqi-Hetao Decoction on Cognitive Function in APP/PS1 Transgenic Mice

Objective This study aimed to explore the effects of Huangqi-Hetao decoction (HH) on cognitive function in amyloid precursor protein/presenilin 1 transgenic (APP/PS1Tg) mice and determine its potential role in attenuating Alzheimer's disease (AD)–related pathology and elucidating the underlying mechanisms. Methods APP/PS1Tg mice were raised to 8 months of age and randomly assigned to the HH group or the AD group. Age-matched C57BL/6 wild-type (WT) mice served as controls. Mice in the HH group received HH daily, whereas the AD and WT groups received no treatment. Results Compared with the AD group, the HH group demonstrated significantly reduced hippocampal expression of Iba-1 ( p < 0.01), NF-κB ( p < 0.01), GFAP ( p < 0.05), and p38 MAPK ( p < 0.005). Malondialdehyde (MDA) levels were significantly reduced ( p < 0.005), whereas NeuN expression was significantly increased ( p < 0.01). In the Morris water maze, mice treated with HH exhibited shorter total swimming distance and escape latency ( p < 0.001), shorter time to first reach the target quadrant ( p < 0.05), reduced average distance to the platform ( p < 0.01), and shorter time from entry to the platform ( p < 0.001) compared with the AD group. Conclusion HH improved cognitive function in APP/PS1 mice. The underlying mechanisms may involve suppression of NF-κB overactivation, inhibition of astrocytic and microglial activation, downregulation of p38 MAPK signaling, reduction of oxidative stress, and MDA accumulation, leading to attenuation of hippocampal pathological changes.