Comparative Neuroprotective Effects of Fermented and Non-Fermented Korean Red Ginseng Extracts in an MPTP-Induced Mouse Model of Parkinson’s Disease

Background Parkinson’s disease (PD) is a multifactorial neurodegenerative disorder characterized by dopaminergic neuronal loss, glial activation, neuroinflammation, and oxidative stress. Fermentation of Korean Red Ginseng Extract (KRGE) alters its ginsenoside composition and may influence biological effects, but direct comparisons with fermented KRGE (F-KRGE) in PD models remain limited. Purpose : To compare the neuroprotective effects of F-KRGE and KRGE in an MPTP-induced mouse model of PD. Methods Ginsenoside compositions were quantitatively characterized by HPLC. Mice received oral F-KRGE or KRGE before and after MPTP administration. Motor performance was assessed using pole, rotarod, and nesting tests. Dopaminergic neuronal integrity and glial activation were evaluated in the substantia nigra pars compacta and striatum. Inflammatory and oxidative stress-related signaling and proinflammatory gene expression were also analyzed. Results F-KRGE and KRGE exhibited distinct ginsenoside profiles. Both formulations attenuated MPTP-induced motor impairment, dopaminergic neuronal loss, and glial activation. Both also modulated TLR4–MyD88–STAT3/MAPK signaling and the Nrf2–NQO1 antioxidant response and reduced proinflammatory gene expression in the striatum. Numerical differences in motor performance and TH expression were observed between the formulations, while the pattern and extent of molecular responses varied across the examined endpoints. Conclusion Both F-KRGE and KRGE exerted neuroprotective effects against MPTP-induced dopaminergic injury, with formulation-dependent differences in ginsenoside composition and biological responses. Further pharmacokinetic and mechanistic studies are warranted to clarify the basis of these differences.