Our previous study demonstrated that gypenosides (Gp) exert protective effects on retinal nerve fibers and axons in a mouse model of experimental autoimmune optic neuritis. However, the therapeutic mechanisms remain unclear. Thus, in this study, a model of oxidative damage in retinal ganglion cells (RGCs) was established to investigate the protective effect of Gp, and its possible influence on oxidative stress in RGCs. Treatment of cells with H 2 O 2 induced RGC injury owing to the generation of intracellular reactive oxygen species (ROS). In addition, the activities of antioxidative enzymes decreased and the expression of inflammatory factors increased, resulting in an increase in cellular apoptosis. Gp helped RGCs to become resistant to oxidation damage by directly reducing the amount of ROS in cells and exerting protective effects against H 2 O 2-induced apoptosis. Treatment with Gp also reduced the generation of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), and increased nuclear respiratory factor 2 (Nrf-2) levels so as to increase the levels of heme oxygenase-1 (HO-1) and glutathione peroxidase 1/2 (Gpx1/2), which can enhance antioxidation in RGCs. In conclusion, our data indicate that neuroprotection by Gp involves its antioxidation and anti-inflammation effects. Gp prevents apoptosis through a mitochondrial apoptotic pathway. This finding might provide novel insights into understanding the mechanism of the neuroprotective effects of gypenosides in the treatment of optic neuritis.

Treatment with gypenosides exerts protective effects on retinal nerve fibers and axons in EAON. When combined with gypenosides, methylprednisolone reduces demyelination in the acute stage of EAON.