Ginseng-Schisandra ameliorates D-galactose-induced cognitive impairment in mice: Evidence from gut microbiota and metabolomic analyses.

Age-related cognitive decline is associated with oxidative stress, systemic inflammation, gut microbial dysbiosis, and metabolic disturbance. This study characterized the chemical profile of a Panax ginseng-Schisandra chinensis co-decoction (TG) and evaluated its effects in a D-galactose-treated mouse model. Chemical constituents were analyzed by liquid chromatography-mass spectrometry. Behavioral performance, serum and brain oxidative-stress markers, serum cytokines, fecal microbiota, short-chain fatty acids (SCFAs), and serum, fecal, and brain metabolites were assessed. Compared with separately prepared extracts, the co-decoction showed a distinctive profile enriched in ginsenoside Rk1. TG-treated mice showed improved performance in behavioral tests, higher superoxide dismutase, glutathione peroxidase, and reduced glutathione values, and lower malondialdehyde values than model mice. TG treatment was also associated with shifts in gut microbial composition, increased fecal acetate, propionate, and butyrate, and changes in tryptophan-, catecholamine-, glycerophospholipid-, and pterin-related metabolites. Targeted liquid chromatography-tandem mass spectrometry (LC-MS/MS) supported group differences in key tryptophan-pathway metabolites. Correlation analyses were exploratory because no association remained significant after false-discovery-rate correction. These findings show that TG administration co-occurred with behavioral, redox, microbial, and metabolic changes in this model; however, the study design does not establish that microbiota or metabolite changes caused the behavioral effects.