Neuroprotective Effects of Propylgallate Against Oxidative Stress in Retinal Ganglion Cells

Abstract Background: Diabetic retinopathy is a group of eye diseases which result in damage to the optic nerve and vision loss, it has seriously affect peoples' health. The purpose of this study is to contrast the neuroprotective effects of curcumin, gastrodin, propylgallate, adenosine. At the same time, we preliminarily explore the molecular mechanism of protective drugs.Methods: In this study, we used 500μM H2O2 treated RGC-5 cells to induce a cellular oxidative stress model. We treated this cell model with four drug monomers: Propylgallate, Curcumin, Gastrodin and Adenosine to find drug monomers with neuroprotective effect. We used apoptosis PCR array to obtain apoptosis related genes regulated by neuroprotective drugs.Results: We found the Propylgallate treated RGC-5 cells had highest survival rate when compared to Curcumin, Gastrodin, Adenosine treated RGC-5 cells.In addition, it had lowest cell cytotoxicity and apoptotic rate when compared to Curcumin, Gastrodin, Adenosine treated RGC-5 cells.Moreover, the expression of ROS in Propylgallate treated RGC-5 cells was lowest when compared to Curcumin, Gastrodin, Adenosine treated RGC-5 cells. We found that Caspase-3, Caspase-8, and Caspase-9 are the main target genes of Propylgallate which can preliminarily explain the neuroprotective mechanism of Propylgallate against apoptosis..Conclusion: The present study revealed that the propylgallate has best neuroprotective effects, it may provide a promissing drug to prevent and improve the damage of optic nerve. In this article, we also preliminarily expounded the neuroprotective molecular mechanism of Propylgallate.

Download Full-text

Artemisinin Attenuated Oxidative Stress and Apoptosis by Inhibiting Autophagy in MPP+-treated SH-SY5Y Cell

10.21203/rs.3.rs-90741/v1 ◽

2020 ◽

Author(s):

Junqiang Yan ◽

Hongxia Ma ◽

Xiaoyi Lai ◽

Jiannan Wu ◽

Anran Liu ◽

...

Keyword(s):

Oxidative Stress ◽

Parkinson’S Disease ◽

Parkinson's Disease ◽

Dopaminergic Neurons ◽

Artemisia Annua ◽

Cell Model ◽

Neuroprotective Effect ◽

Critical Role ◽

Neuroprotective Effects ◽

Pre Treatment

Abstract Background Parkinson's disease (PD) is the second most common neurodegenerative disease after Alzheimer's. The drugs currently used to treat PD cannot inhibit the development of PD, and long-term use produces severe drug resistance and adverse reaction. Artemisinin (ART) is an active ingredient of Artemisia annua and has a neuroprotective effect, but the mechanism is still unclear. This study was designed to investigate the neuroprotective effect of ART in MPP+-treated SH-SY5Y cells. Results There was no significant cytotoxicity when the ART concentration was under. 40μM. The 20μM ART for 24h could increase the cell viability by reducing oxidative stress and cell apoptosis in MPP+-treated SH-SY5Y cell. In addition, immunoblot and immunofluorescence results showed that MPP+ treatment increased the expression of Beclin1, LC3II/LC3I and decreased the expression of P62, while ART can reverse the changes caused by MPP+. Discussion More and more researches reported that ART and its derivates have neuroprotective effects through anti-oxidant and anti-apoptosis. we found that pre-treated cells with 20μM ART for 4h could significantly increase the viability in Parkinson's disease cell model. The oxidative stress and apoptosis were the main reason for the degeneration of dopaminergic neurons, while artemisinin can attenuate oxidative stress and apoptosis in MPP+-lesioned dopaminergic neurons. The levels of autophagy proteins LC3II/I, Beclin1 and P62 also showed that MPP+ increased the autophagy level, and pre-treatment with ART decreased the autophagy level, which may be the pathological mechanism for artemisinin to reduce oxidative stress damage and apoptosis. Conclusions These results indicate that ART exerts a positive effect on MPP+-treated SH-SY5Y cells in terms of anti-oxidative stress and anti-apoptosis. These effects may be related to autophagy. These findings contribute to a better understanding of the critical role of ART in PD treatment.

Download Full-text

Neuroprotection: A Valuable Goal in Glaucoma Management?

European Journal of Ophthalmology ◽

10.1177/1120672107017005s06 ◽

2007 ◽

Vol 17 (5_suppl) ◽

pp. 24-27

Author(s):

L. Rossetti

Keyword(s):

Clinical Trial ◽

Optic Nerve ◽

Animal Models ◽

Ganglion Cells ◽

Neuroprotective Effect ◽

Disease Process ◽

Clinical Trial Data ◽

Nerve Degeneration ◽

Neuroprotective Effects ◽

Patients Experience

Glaucoma is characterized by an accelerated loss of retinal ganglion cells, as a result of damage to optic nerve axons. One factor involved in the disease process is elevated intraocular pressure (IOP) and this is the current focus of therapies. However, up to 45% of patients experience glaucoma progression despite good IOP control and partly as a result, the treatment principle of direct neuroprotection has been developed, which consists of treating optic nerve degeneration in glaucoma independently of IOP lowering. Animal models have shown the potential of this approach but there are limited clinical trial data. Brimonidine and memantine currently show promise, in terms of efficacy and side effects, among the compounds entering clinical trials. Brimonidine has been shown to have a neuroprotective effect independent of IOP lowering in humans with glaucoma, and data from a large clinical trial are being analyzed. Memantine has shown neuroprotective effects in animal models of glaucoma, and data from a clinical trial in humans are awaited.

Download Full-text

Targeting Oxidative Stress for Treatment of Glaucoma and Optic Neuritis

Oxidative Medicine and Cellular Longevity ◽

10.1155/2017/2817252 ◽

2017 ◽

Vol 2017 ◽

pp. 1-8 ◽

Cited By ~ 45

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.

Download Full-text

Artemisinin attenuated oxidative stress and apoptosis by inhibiting autophagy in MPP+-treated SH-SY5Y cell

10.21203/rs.3.rs-64841/v1 ◽

2020 ◽

Author(s):

Junqiang Yan ◽

Hongxia Ma ◽

Xiaoyi Lai ◽

Jiannan Wu ◽

Anran Liu ◽

...

Keyword(s):

Oxidative Stress ◽

Parkinson’S Disease ◽

Parkinson's Disease ◽

Dopaminergic Neurons ◽

Artemisia Annua ◽

Cell Model ◽

Neuroprotective Effect ◽

Critical Role ◽

Neuroprotective Effects ◽

Pre Treatment

Abstract Background Parkinson's disease (PD) is the second most common neurodegenerative disease after Alzheimer's. The drugs currently used to treat PD cannot inhibit the development of PD, and long-term use produces severe drug resistance and adverse reaction. Artemisinin (ART) is an active ingredient of Artemisia annua and has a neuroprotective effect, but the mechanism is still unclear. This study was designed to investigate the neuroprotective effect of ART in MPP+-treated SH-SY5Y cells. Results There was no significant cytotoxicity when the ART concentration was under. 40 µM. The 20 µM ART for 24 h could increase the cell viability by reducing oxidative stress and cell apoptosis in MPP+-treated SH-SY5Y cell. In addition, immunoblot and immunofluorescence results showed that MPP+ treatment increased the expression of Beclin1, LC3II/LC3I and decreased the expression of P62, while ART can reverse the changes caused by MPP+. Discussion More and more researches reported that ART and its derivates have neuroprotective effects through anti-oxidant and anti-apoptosis. we found that pre-treated cells with 20 µM ART for 4 h could significantly increase the viability in Parkinson's disease cell model. The oxidative stress and apoptosis were the main reason for the degeneration of dopaminergic neurons, while artemisinin can attenuate oxidative stress and apoptosis in MPP+-lesioned dopaminergic neurons. The levels of autophagy proteins LC3II/I, Beclin1 and P62 also showed that MPP + increased the autophagy level, and pre-treatment with ART decreased the autophagy level, which may be the pathological mechanism for artemisinin to reduce oxidative stress damage and apoptosis. Conclusions These results indicate that ART exerts a positive effect on MPP+-treated SH-SY5Y cells in terms of anti-oxidative stress and anti-apoptosis. These effects may be related to autophagy. These findings contribute to a better understanding of the critical role of ART in PD treatment.

Download Full-text

Neurotherapeutic Effect of Inula britannica var. Chinensis against H2O2-Induced Oxidative Stress and Mitochondrial Dysfunction in Cortical Neurons

Antioxidants ◽

10.3390/antiox10030375 ◽

2021 ◽

Vol 10 (3) ◽

pp. 375

Author(s):

Jin Young Hong ◽

Hyunseong Kim ◽

Junseon Lee ◽

Wan-Jin Jeon ◽

Seung Ho Baek ◽

...

Keyword(s):

Oxidative Stress ◽

Mitochondrial Dysfunction ◽

Cortical Neurons ◽

Inflammatory Diseases ◽

Neuroprotective Effect ◽

Neuroprotective Effects ◽

Neuronal Viability ◽

Inula Britannica ◽

Oxidative Effects

Inula britannica var. chinensis (IBC) has been used as a traditional medicinal herb to treat inflammatory diseases. Although its anti-inflammatory and anti-oxidative effects have been reported, whether IBC exerts neuroprotective effects and the related mechanisms in cortical neurons remain unknown. In this study, we investigated the effects of different concentrations of IBC extract (5, 10, and 20 µg/mL) on cortical neurons using a hydrogen peroxide (H2O2)-induced injury model. Our results demonstrate that IBC can effectively enhance neuronal viability under in vitro-modeled reaction oxygen species (ROS)-generating conditions by inhibiting mitochondrial ROS production and increasing adenosine triphosphate level in H2O2-treated neurons. Additionally, we confirmed that neuronal death was attenuated by improving the mitochondrial membrane potential status and regulating the expression of cytochrome c, a protein related to cell death. Furthermore, IBC increased the expression of brain-derived neurotrophic factor and nerve growth factor. Furthermore, IBC inhibited the loss and induced the production of synaptophysin, a major synaptic vesicle protein. This study is the first to demonstrate that IBC exerts its neuroprotective effect by reducing mitochondria-associated oxidative stress and improving mitochondrial dysfunction.

Download Full-text

Artemisinin attenuated oxidative stress and apoptosis by inhibiting autophagy in MPP+-treated SH-SY5Y cells

Journal of Biological Research-Thessaloniki ◽

10.1186/s40709-021-00137-6 ◽

2021 ◽

Vol 28 (1) ◽

Author(s):

Junqiang Yan ◽

Hongxia Ma ◽

Xiaoyi Lai ◽

Jiannan Wu ◽

Anran Liu ◽

...

Keyword(s):

Oxidative Stress ◽

Membrane Potential ◽

Protein Expression ◽

Mitochondrial Membrane Potential ◽

Western Blotting ◽

Cell Apoptosis ◽

Mitochondrial Membrane ◽

Caspase 3 ◽

Neuroprotective Effect ◽

Neuroprotective Effects

Abstract Background Parkinson’s disease (PD) is the second most common neurodegenerative disease after Alzheimer's disease. The oxidative stress is an important component of the pathogenesis of PD. Artemisinin (ART) has antioxidant and neuroprotective effects. The purpose of this study is to explore the neuroprotective effect of ART on 1-methyl-4-phenyliodine iodide (MPP +)-treated SH-SY5Y cells and underlying mechanism. Methods We used MPP+-treated SH-SY5Y cells to study the neuroprotective effect of ART. Cell viability was measured by MTT assay after incubating the cells with MPP+ and/or ART for 24 h. DCFH-DA was used to detect the level of intracellular reactive oxygen species (ROS), and WST-8 was used to detect the level of superoxide dismutase (SOD). The level of intracellular reduced glutathione (GSH) was detected with 5,5΄-dithiobis-(2-nitrobenzoic acid), and the level of malondialdehyde (MDA) was assessed based on the reaction of MDA and thiobarbituric acid. A mitochondrial membrane potential detection kit (JC-1) was used to detect changes in the mitochondrial membrane potential (MMP), and an Annexin V-FITC cell apoptosis kit was used to detect cell apoptosis. The expression levels of caspase-3, cleaved caspase-3 and the autophagy-related proteins LC3, beclin-1, and p62 were detected by Western blotting. In addition, to verify the change in autophagy, we used immunofluorescence to detect the expression of LC3 and p62. Results No significant cytotoxicity was observed at ART concentrations up to 40 μM. ART could significantly increase the viability of SH-SY5Y cells treated with MPP+ and reduce oxidative stress damage and apoptosis. In addition, the Western blotting and immunofluorescence results showed that MPP+ treatment could increase the protein expression of beclin1 and LC3II/LC3I and decrease the protein expression of p62, indicating that MPP+ treatment could induce autophagy. Simultaneous treatment with ART and MPP+ could decrease the protein expression of beclin1 and LC3II/LC3I and increase the protein expression of p62, indicating that ART could decrease the level of autophagy induced by MPP+. Conclusion Our results indicate that ART has a protective effect on MPP+-treated SH-SY5Y cells by the antioxidant, antiapoptotic activities and inhibition of autophagy. Our findings may provide new hope for the prevention and treatment of PD.

Download Full-text

Oxidative Stress in Optic Neuropathies

Antioxidants ◽

10.3390/antiox10101538 ◽

2021 ◽

Vol 10 (10) ◽

pp. 1538

Author(s):

Berta Sanz-Morello ◽

Hamid Ahmadi ◽

Rupali Vohra ◽

Sarkis Saruhanian ◽

Kristine Karla Freude ◽

...

Keyword(s):

Oxidative Stress ◽

Optic Neuropathy ◽

Vision Loss ◽

Ganglion Cells ◽

Redox System ◽

Ischemic Optic Neuropathy ◽

Retinal Ganglion ◽

Oxidative Stress Biomarkers ◽

Optic Disc Drusen ◽

Advanced Stages

Increasing evidence indicates that changes in the redox system may contribute to the pathogenesis of multiple optic neuropathies. Optic neuropathies are characterized by the neurodegeneration of the inner-most retinal neurons, the retinal ganglion cells (RGCs), and their axons, which form the optic nerve. Often, optic neuropathies are asymptomatic until advanced stages, when visual impairment or blindness is unavoidable despite existing treatments. In this review, we describe systemic and, whenever possible, ocular redox dysregulations observed in patients with glaucoma, ischemic optic neuropathy, optic neuritis, hereditary optic neuropathies (i.e., Leber’s hereditary optic neuropathy and autosomal dominant optic atrophy), nutritional and toxic optic neuropathies, and optic disc drusen. We discuss aspects related to anti/oxidative stress biomarkers that need further investigation and features related to study design that should be optimized to generate more valuable and comparable results. Understanding the role of oxidative stress in optic neuropathies can serve to develop therapeutic strategies directed at the redox system to arrest the neurodegenerative processes in the retina and RGCs and ultimately prevent vision loss.

Download Full-text

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

Journal of Molecular Neuroscience ◽

10.1007/s12031-019-01468-9 ◽

2020 ◽

Vol 70 (4) ◽

pp. 618-630 ◽

Cited By ~ 1

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.

Download Full-text

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

Evidence-based Complementary and Alternative Medicine ◽

10.1093/ecam/nek005 ◽

2006 ◽

Vol 3 (1) ◽

pp. 71-77 ◽

Cited By ~ 41

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.

Download Full-text