Aspergillus oryzae solid-state fermentation enriches protopanaxatriol-type ginsenosides in Panax ginseng and confers cytoprotective effects in vitro

Background This study established and optimized a food-grade solid-state fermentation (SSF) process using Aspergillus oryzae to biotransform ginsenosides in five-year-old white ginseng roots. Methods Through single-factor and orthogonal tests, optimal SSF conditions were identified. UPLC-QTOF-MS/MS analysis was used to characterize ginsenoside profile changes. In an ethanol-induced injury model using GES-1 gastric epithelial cells, the fermented extract was evaluated for cytoprotective effects. Results Optimal SSF conditions were fermentation time of 8 days, inoculum size of 2.5%, and temperature of 28°C. UPLC-QTOF-MS/MS analysis revealed significant remodeling of protopanaxatriol (PPT)-type ginsenosides, with ginsenoside Rf and PPT increasing by 3.55-fold and 5.03-fold, respectively ( p < 0.05). In the ethanol-induced injury model using GES-1 gastric epithelial cells, the fermented extract demonstrated dose-dependent anti-inflammatory, antioxidant, and anti-apoptotic effects without cytotoxicity. We hypothesize that the extracellular glycosidase activity of A. oryzae mediates the sequential deglycosylation leading to the observed PPT-type enrichment, although the specific enzymes involved require further identification. Overall, these results provide a proof-of-concept for a food-safe SSF platform tailored to whole white ginseng roots. This process effectively remodels the ginsenoside profile to enrich cytoprotective PPT-type compounds, supporting its potential for nutraceutical development.