Gypenosides Prevent H2O2-Induced Retinal Ganglion Cell Apoptosis by Concurrently Suppressing the Neuronal Oxidative Stress and Inflammatory Response

Abstract

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.

Gypenosides Alleviate Cone Cell Death in a Zebrafish Model of Retinitis Pigmentosa

“…The antioxidant defense system was also compromised in rpgrip1 mutant eyes, demonstrating a marked decrease in expression of antioxidant genes and in activities of antioxidant enzymes (Figures 4 and 5). Previous studies have shown Gyp's protection against oxidative damage in vitro and in vivo [18,19,21,[41][42][43][44]. Here we have demonstrated that Gyp treatment can suppress ROS production, upregulated antioxidant gene expression and increased antioxidant enzyme activities and GSH level in rigrip1 mutant eyes (Figures 4 and 5).…”

“…In contrast Gyp also has a toxic effect against cancer at high concentrations by inducing apoptosis and cell cycle arrest and through the inhibition of proliferation and DNA repair [17]. Recent studies have shown Gyp inhibited H 2 O 2induced oxidative damage and inflammation in the retinal pigment epithelial (RPE) and the ganglion cells [18,19]. Gyp also reduces inflammation, demyelination and axonal loss in the optic nerve of the optic neuritis mouse model [20].…”

Gypenosides Inhibit Inflammatory Response and Apoptosis of Endothelial and Epithelial Cells in LPS-Induced ALI: A Study Based on Bioinformatic Analysis and in vivo/vitro Experiments

“… 33 However, lower dosage of GPs exerted an anti-apoptosis effect. 12 , 13 The present study revealed that GPs at 10 μg/mL effectively restrained the apoptosis of the HPMEC and MLE-12 induced by LPS challenge. LPS challenge up-regulated the expression of Bax (a pro-apoptotic protein) and cleaved caspase-3 (an apoptotic effector protein), down-regulated Bcl-2 (an anti-apoptotic protein) in HPMEC, indicating LPS-induced apoptosis in HPMEC.…”

“…Some studies have revealed GPs inhibited the apoptosis induced by oxidative stress. 12 , 13 Whether GPs improve lung injury during ALI and the mechanism remains unclear. The study was conducted to investigate potential therapeutic mechanisms of GPs on ALI and provide novel treatments for ALI.…”

Oleacein Attenuates the Pathogenesis of Experimental Autoimmune Encephalomyelitis through Both Antioxidant and Anti-Inflammatory Effects

“…Prominent ROS accumulation in the optic nerve contributes to RGCs apoptosis and axonal loss, being the major cause of visual loss in EAE/MS disease. It has been reported that RGCs, whose axons contribute to the ON, are highly dependent on oxidative phosphorylation and increasing antioxidant defenses against superoxide provides neuroprotection [ 52 ]. In our in vitro study, the presence of OLE, clearly diminished both ROS production and, consequently, apoptosis of neuronal cells (RGC-5 cells), supporting the axis “ROS-cell loss”.…”