LC-MS-based metabolomics reveals the In Vivo effects of cognitive formula 1 in rats with Aβ-induced Alzheimer's disease.

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive impairment of cognition, behavior, and functional abilities that can ultimately lead to death. Cognitive Formula 1 (CF1), a traditional Chinese medicine (TCM) formulation, has demonstrated promising therapeutic efficacy in clinical applications. However, the precise mechanisms underlying its therapeutic effects in AD remain unclear. An AD rat model was established by intracerebral injection of amyloid-β peptide 1-42 (Aβ₁₋₄₂) to investigate the mechanism of CF1. The results indicated that synergistic interactions among multiple CF1 components influence host metabolic pathways, in particular those involved in glycerophospholipid and amino acid metabolism, thereby suggesting an explanation for the alleviation of systemic metabolic dysregulation by the formulation. CF1 also remodeled the gut microbiota by reducing the abundance of potentially detrimental bacteria, such as Veillonella and Lachnoclostridium, while enhancing that of beneficial bacteria, such as Roseburia. These changes improved intestinal homeostasis, reduced endotoxin influx, and alleviated systemic inflammation. The concurrent improvements in host metabolism and gut microbial composition prevented peripheral pro-inflammatory and oxidative stress signals from reaching the brain, thus inhibiting overactivation of hippocampal microglia and attenuating neuroinflammation. These effects preserved neuronal structure and function, ultimately enhancing learning, memory, and spatial cognition in AD model rats.