Protective Effects of Praeparatus Gardenia Fructus Oil and Its Active Constituents Against Oxidative Neurodegeneration: Evidence from In Vitro and In Vivo Studies

Neurodegenerative disorders demand safe, multi-targeted interventions. We revealed praeparatus Gardenia Fructus oil (PGFO) as a novel neuroprotective functional oil, outperforming raw and stir-baked Gardenia Fructus oil, as well as conventional edible oils. In H₂O₂-injured PC12 cells, PGFO restored redox balance and enhanced antioxidant enzymes, with effects stronger than those of isolated fractions, suggesting synergistic bioavailability within the oil matrix. Transcriptomics indicated modulation of the neuroactive ligand-receptor interaction and tryptophan pathways might be involved in its protective mechanism. In APP/PS1 mice, PGFO improved cognition, preserved neuronal integrity, reduced oxidative stress and neuroinflammation, and reshaped gut microbiota with elevated short-chain fatty acids. The study provides a theoretical basis for the development of PGFO as a neuroprotective dietary ingredient. These findings establish PGFO as a prototype functional oil integrating lipid-based delivery, neuromodulation, and gut–brain signaling, providing a promising dietary strategy against Alzheimer’s disease.