Ginseng under forest exerts stronger anti-aging effects compared to garden ginseng probably via regulating PI3K/AKT/mTOR pathway, SIRT1/NF-κB pathway and intestinal flora

Ginseng is deemed to be an effective anti-aging therapy. Evidence for differences in representative active ingredients and anti-aging effects between garden ginseng (GG) and ginseng under forest (FG) is insufficient.The study was designed to systematically analyze the differences in the mechanistic protective effects of GG and FG on aging mice based on their compositional differences.The chemical ingredients in GG and FG were first determined. In vivo, D-galactose-induced aging mice were orally administered GG or FG (400 mg/kg/day) for 6 weeks. Behavioral parameters of mice were measured by the radial 8-arm maze, and the changes in body weight and organ indices were recorded. Blood, brain tissue, and feces were collected for biochemical analysis, histopathological staining, Western blotting, and 16S rDNA intestinal flora sequencing, respectively.The absolute contents of total ginsenosides, polyphenols, crude polysaccharides, starch, and protein in GG were 0.71, 0.68, 1.15, 2.27, and 1.08 folds higher than those in FG, respectively; while FG exhibited a higher relative abundance of representative active ingredients (total ginsenosides, polyphenols, crude polysaccharides, and protein) but lower relative content of starch than GG. GG and FG improved hippocampal lesions and poor weight gain, organ indices, and behavioral indices, and prevented excessive oxidative stress and acetylcholinesterase activity in aging mice. What's more, GG and FG treatment ameliorated excessive apoptosis and inflammatory reaction in the aging brain by modulating apoptosis-related proteins, PI3K/AKT/mTOR pathway, and SIRT1/NF-κB pathway. GG and FG also restored the diversity and structure of gut microbiota, up-regulated the relative abundance of beneficial bacteria (e.g., Lactobacillus), and tended to exert key anti-aging effects via the microbiota-gut-brain axis. Notably, in vivo experiments confirmed that FG had a stronger anti-aging activity than GG.FG exerts a more powerful anti-aging effect than GG by regulating oxidative stress, apoptosis, inflammation, and the microbe-gut-brain axis, possibly relying on the higher relative abundance of representative active ingredients (total ginsenosides, polyphenols, crude polysaccharides, and protein) in FG.