Increasing minor ginsenosides contents and enhancing neuroprotective effects of total ginsenosides fermented by Lactiplantibacillus plantarum

Minor ginsenosides have been proven to have higher pharmacological activity than the major ginsenosides. The transformation of major ginsenosides to minor ginsenosides by lactic acid bacteria was considered to be a promising method. Therefore, this study focuses on utilizing glycosidase-producing Lactiplantibacillus plantarum GLP40 to transform total ginsenosides (TG) and increase the content of minor ginsenosides, as well as investigate the neuroprotective effects of fermented total ginsenosides (FTG). After 21d fermentation, the transformation products were purified using D101 macroporous resin column chromatography, and identified by HPLC and LC-MS analyses. The neuroprotective effect of FTG was evaluated using MPTP-induced neural injury mice model. Lact. plantarum GLP40 fermentation increased the contents of minor ginsenosides in TG, such as Rg3, Rh2, CK, and Rk3. FTG showed stronger alleviation of 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine Hydrochloride (MPTP) induced memory loss and dyskinesia in mice, and inhibited tyrosine hydroxylase (TH) depletion and ionized calcium binding adapter molecule 1 (Iba-1) production than TG. Further, FTG significantly increased serum IL-10 levels and inhibited the expression of pro-inflammatory cytokines compared to TG. Moreover, FTG treatment activated the anti-apoptotic PI3K/AKT/mTOR signaling pathway and inhibited the expression of the inflammatory NF-κB/COX-2/iNOS pathway. In conclusion, Lact. plantarum GLP40 fermentation enhances the neuroprotective effects of total ginsenosides by increasing minor ginsenosides. FTG protected MPTP induced neural injury in mice by regulating inflammation and cell apoptosis signaling pathways.