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

2020 ◽  
Vol 70 (4) ◽  
pp. 618-630 ◽  
Author(s):  
Hong-Kan Zhang ◽  
Yuan Ye ◽  
Kai-Jun Li ◽  
Zhen-ni Zhao ◽  
Jian-Feng He
Keyword(s):  
Oxidative Stress ◽  
Optic Neuritis ◽  
Ganglion Cells ◽  
Nerve Fibers ◽  
Inflammatory Factors ◽  
Heme Oxygenase 1 ◽  
Protective Effects ◽  
Retinal Ganglion ◽  
Apoptotic Pathway ◽  
Neuroprotective Effects

AbstractOur 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 H2O2 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 H2O2-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.

scholarly journals Brazilian Green Propolis Protects against Retinal Damage In Vitro and In Vivo

2006 ◽  
Vol 3 (1) ◽  
pp. 71-77 ◽  
Author(s):  
Yuta Inokuchi ◽  
Masamitsu Shimazawa ◽  
Yoshimi Nakajima ◽  
Shinsuke Suemori ◽  
Satoshi Mishima ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Retinal Ganglion Cells ◽  
Ganglion Cells ◽  
Water Soluble ◽  
Retinal Damage ◽  
Retinal Ganglion ◽  
Neuroprotective Effects ◽  
Brazilian Green Propolis

Propolis, a honeybee product, has gained popularity as a food and alternative medicine. Its constituents have been shown to exert pharmacological (anticancer, antimicrobial and anti-inflammatory) effects. We investigated whether Brazilian green propolis exerts neuroprotective effects in the retinain vitroand/orin vivo.In vitro, retinal damage was induced by 24 h hydrogen peroxide (H2O2) exposure, and cell viability was measured by Hoechst 33342 and YO-PRO-1 staining or by a resazurin–reduction assay. Propolis inhibited the neurotoxicity and apoptosis induced in cultured retinal ganglion cells (RGC-5, a rat ganglion cell line transformed using E1A virus) by 24 h H2O2 exposure. Propolis also inhibited the neurotoxicity induced in RGC-5 cultures by staurosporine. Regarding the possible underlying mechanism, in pig retina homogenates propolis protected against oxidative stress (lipid peroxidation), as also did trolox (water-soluble vitamin E). In micein vivo, propolis (100 mg kg−1; intraperitoneally administered four times) reduced the retinal damage (decrease in retinal ganglion cells and in thickness of inner plexiform layer) induced by intravitrealin vivo N-methyl-d-aspartate injection. These findings indicate that Brazilian green propolis has neuroprotective effects against retinal damage bothin vitroandin vivo, and that a propolis-induced inhibition of oxidative stress may be partly responsible for these neuroprotective effects.

Docosahexaenoic acid (DHA) has neuroprotective effects against oxidative stress in retinal ganglion cells

2009 ◽  
Vol 1251 ◽  
pp. 269-275 ◽  
Author(s):  
Masamitsu Shimazawa ◽  
Yoshimi Nakajima ◽  
Yukihiko Mashima ◽  
Hideaki Hara
Keyword(s):  
Oxidative Stress ◽  
Docosahexaenoic Acid ◽  
Retinal Ganglion Cells ◽  
Ganglion Cells ◽  
Retinal Ganglion ◽  
Neuroprotective Effects

scholarly journals Hesperetin protects SH-SY5Y cells against 6- hydroxydopamine-induced neurotoxicity via activation of NRF2/ARE signaling pathways

2020 ◽  
Vol 19 (6) ◽  
pp. 1197-1201 ◽  
Author(s):  
Jing Li ◽  
Yue Liu ◽  
Li Wang ◽  
Zhaowei Gu ◽  
Zhigang Huan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cell Viability ◽  
Heme Oxygenase 1 ◽  
Protective Effects ◽  
Neuroprotective Effects ◽  
Ldh Release ◽  
6 Hydroxydopamine

Purpose: To investigation the protective effects of hesperetin against 6-hydroxydopamine (6-OHDA)- induced neurotoxicity. Methods: SH-SY5Y cells were incubated with 6-OHDA to create an in vitro model of neurotoxicity. This model was used to test the neuroprotective effects of hesperetin. Cell viability was assessed by MTT and lactate dehydrogenase (LDH) release assays. Flow cytometry and western blot were used to quantify apoptosis. Oxidative stress was evaluated by determining intracellular glutathione (GSH), malondialdehyde (MDA), superoxide dismutase (SOD), and reactive oxygen species (ROS). Results: In SH-SY5Y cells, treatment with 6-OHDA decreased cell viability and promoted LDH release. However, exogenous hesperetin protected against 6-OHDA-mediated toxicity. Similarly, although incubation with 6-OHDA induced apoptosis and increased cleaved caspase-3 and -9 levels, treatment with hesperetin protected against these effects. Treatment with 6-OHDA also led to significant oxidative stress, as indicated by reduced GSH and SOD levels and increased MDA and ROS levels in SH-SY5Y cells. However, these changes were reversed by pre-treatment with hesperetin. Of interest, hesperetin led to changes in 6-OHDA-induced expression of NRF2, heme oxygenase-1 (HO-1), glutamate-cysteine ligase (GCL) catalytic subunit (GCLC), and GCL modulatory (GCLM). Conclusion: Hesperetin protects against cell toxicity, apoptosis, and oxidative stress via activation of NRF2 pathway in a 6-OHDA-induced model of neurotoxicity. Future studies should investigate the use of hesperetin as a potential therapeutic approach for prevention or management of Parkinson’s disease. Keywords: Hesperetin, 6-OHDA, Neurotoxicity, NRF2, Parkinson’s disease

scholarly journals Rutin prevents retinal ganglion cell death and exerts protective effects by regulating transforming growth factor-β2/Smad2/3Akt/PTEN signaling in experimental rat glaucoma

2021 ◽  
Vol 18 (5) ◽  
pp. 985-993
Author(s):  
Ying Li ◽  
Leilei Qin ◽  
Liang Ying ◽  
Hanguang Dong ◽  
Dabo Wang
Keyword(s):  
Protective Effect ◽  
Rat Model ◽  
Transforming Growth Factor ◽  
Ganglion Cells ◽  
Protective Effects ◽  
Retinal Ganglion ◽  
Sprague Dawley ◽  
Apoptotic Pathway ◽  
Ganglion Cell Death

Purpose: To investigate the protective effect of rutin against glaucoma in a rat model, and the mechanisms involved. Methods: Sprague-Dawley rats were injected hypertonic saline in the limbal vein for elevation of intraocular pressure (IOP). Rats in the treatment group were administered rutin at doses of 12.5, 25 or 50 mg/kg orally and daily for 21 days. Results: Rutin markedly (p < 0.05) reduced IOP and prevented loss of retinal ganglion cells (RGCs). The expression of apoptotic pathway proteins, i.e., Bcl-xL, Bcl-2, Bad and Bax were significantly (p < 0.05) regulated by rutin. Moreover, rutin caused a substantial decrease in TGF-β2 expression, and also down-regulated p-Smad2 and p-Smad3 dose-dependently (p < 0.05). Raised levels of collagen I, fibronectin and elastin were effectively down-regulated. Rutin substantially up-regulated the Akt pathway involved in cell survival, and markedly improved the survival of RGCs subjected to hypoxia in vitro (p < 0.05). Conclusion: These results reveal that rutin exerts protective effect against glaucoma in a rat model via a mechanism involving regulation of the TGF-β2/Smad2/3Akt/PTEN signaling pathways. Thus, rutin has potentials for use in the management of glaucoma.

scholarly journals Thymoquinone Prevents Dopaminergic Neurodegeneration by Attenuating Oxidative Stress Via the Nrf2/ARE Pathway

2021 ◽  
Vol 11 ◽  
Author(s):  
Jianjian Dong ◽  
Xiaoming Zhang ◽  
Shijing Wang ◽  
Chenchen Xu ◽  
Manli Gao ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nuclear Translocation ◽  
Nigella Sativa ◽  
Drug Candidate ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Protective Effects ◽  
Quinone Oxidoreductase ◽  
Neuroprotective Effects ◽  
Antioxidant Genes

Studies have indicated that oxidative stress plays a crucial role in the development of Parkinson’s disease (PD) and other neurodegenerative conditions. Research has also revealed that nuclear factor erythroid 2-related factor 2 (Nrf2) triggers the expression of antioxidant genes via a series of antioxidant response elements (AREs), thus preventing oxidative stress. Thymoquinone (TQ) is the bioactive component of Nigella sativa, a medicinal plant that exhibits antioxidant and neuroprotective effects. In the present study we examined whether TQ alleviates in vivo and in vitro neurodegeneration induced by 1-methyl-4-phenylpyridinium (MPP+) and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) by acting as an activator of the Nrf2/ARE cascade. We showed that TQ significantly reduced MPP+-mediated cell death and apoptosis. Moreover, TQ significantly elevated the nuclear translocation of Nrf2 and significantly increased the subsequent expression of antioxidative genes such as Heme oxygenase 1 (HO-1), quinone oxidoreductase (NQO1) and Glutathione-S-Transferase (GST). The application of siRNA to silence Nrf2 led to an abolishment in the protective effects of TQ. We also found that the intraperitoneal injection of TQ into a rodent model of PD ameliorated oxidative stress and effectively mitigated nigrostriatal dopaminergic degeneration by activating the Nrf2-ARE pathway. However, these effects were inhibited by the injection of a lentivirus wrapped Nrf2 siRNA (siNrf2). Collectively, these findings suggest that TQ alleviates progressive dopaminergic neuropathology by activating the Nrf2/ARE signaling cascade and by attenuating oxidative stress, thus demonstrating that TQ is a potential novel drug candidate for the treatment of PD.

scholarly journals Targeting Oxidative Stress for Treatment of Glaucoma and Optic Neuritis

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Atsuko Kimura ◽  
Kazuhiko Namekata ◽  
Xiaoli Guo ◽  
Takahiko Noro ◽  
Chikako Harada ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Optic Nerve ◽  
Optic Neuritis ◽  
Vision Loss ◽  
Demyelinating Disease ◽  
Ganglion Cells ◽  
Retinal Ganglion ◽  
Progressive Degeneration ◽  
Elevated Intraocular Pressure ◽  
The Central Nervous System

Glaucoma is a neurodegenerative disease of the eye and it is one of the leading causes of blindness. Glaucoma is characterized by progressive degeneration of retinal ganglion cells (RGCs) and their axons, namely, the optic nerve, usually associated with elevated intraocular pressure (IOP). Current glaucoma therapies target reduction of IOP, but since RGC death is the cause of irreversible vision loss, neuroprotection may be an effective strategy for glaucoma treatment. One of the risk factors for glaucoma is increased oxidative stress, and drugs with antioxidative properties including valproic acid and spermidine, as well as inhibition of apoptosis signal-regulating kinase 1, an enzyme that is involved in oxidative stress, have been reported to prevent glaucomatous retinal degeneration in mouse models of glaucoma. Optic neuritis is a demyelinating inflammation of the optic nerve that presents with visual impairment and it is commonly associated with multiple sclerosis, a chronic demyelinating disease of the central nervous system. Although steroids are commonly used for treatment of optic neuritis, reduction of oxidative stress by approaches such as gene therapy is effective in ameliorating optic nerve demyelination in preclinical studies. In this review, we discuss oxidative stress as a therapeutic target for glaucoma and optic neuritis.

scholarly journals Neuroprotective effects of Argon are mediated via an ERK-1/2 dependent regulation of heme-oxygenase-1 in retinal ganglion cells

2015 ◽  
Vol 134 (4) ◽  
pp. 717-727 ◽  
Author(s):  
Felix Ulbrich ◽  
Kai B. Kaufmann ◽  
Mark Coburn ◽  
Wolf Alexander Lagrèze ◽  
Martin Roesslein ◽  
...  
Keyword(s):  
Retinal Ganglion Cells ◽  
Heme Oxygenase ◽  
Ganglion Cells ◽  
Heme Oxygenase 1 ◽  
Retinal Ganglion ◽  
Neuroprotective Effects

scholarly journals The Role of Transforming Growth Factor-Beta in Retinal Ganglion Cells with Hyperglycemia and Oxidative Stress

2020 ◽  
Vol 21 (18) ◽  
pp. 6482
Author(s):  
Hsin-Yi Chen ◽  
Yi-Jung Ho ◽  
Hsiu-Chuan Chou ◽  
En-Chi Liao ◽  
Yi-Ting Tsai ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Diabetic Retinopathy ◽  
Growth Factor ◽  
Retinal Ganglion Cells ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Ganglion Cells ◽  
Heme Oxygenase 1 ◽  
Retinal Ganglion ◽  
Growth Factor Beta

A characteristic of diabetes mellitus is hyperglycemia, which is considered with an emphasis on the diabetic retinopathy of progressive neurodegenerative disease. Retinal ganglion cells (RGCs) are believed to be important cells affected in the pathogenesis of diabetic retinopathy. Transforming growth factor-beta (TGF-β) is a neuroprotective protein that helps to withstand various neuronal injuries. To investigate the potential roles and regulatory mechanisms of TGF-β in hyperglycemia-triggered damage of RGCs in vitro, we established RGCs in 5.5, 25, 50, and 100 mM D-glucose supplemented media and focused on the TGF-β-related oxidative stress pathway in combination with hydrogen peroxide (H2O2). Functional experiments showed that TGF-β1/2 protein expression was upregulated in RGCs with hyperglycemia. The knockdown of TGF-β enhanced the accumulation of reactive oxygen species (ROS), inhibited the cell proliferation rate, and reduced glutathione content in hyperglycemia. Furthermore, the results showed that the TGF-β-mediated enhancement of antioxidant signaling was correlated with the activation of stress response proteins and the antioxidant pathway, such as aldehyde dehydrogenase 3A1 (ALDH3A1), heme oxygenase-1 (HO-1), nuclear factor erythroid 2-related factor (Nrf2), and hypoxia-inducible factor (HIF-1α). Summarizing, our results demonstrated that TGF-β keeps RGCs from hyperglycemia-triggered harm by promoting the activation of the antioxidant pathway, suggesting a potential anti-diabetic therapy for the treatment of diabetic retinopathy.

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