Gypenosides protect retinal pigment epithelium cells from oxidative stress

Alhasani, Reem Hasaballah; Biswas, Lincoln; Tohari, Ali Mohammad; Zhou, Xiaohu; Reilly, James; He, Jianfeng; Shu, Xinhua

doi:10.1016/j.fct.2017.12.037

Cited by 36 publications

(44 citation statements)

References 52 publications

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“…Specifically, the antioxidative effect of Gp can reduce the production of ROS, increase the expressions of Nrf-2/ARE and OH-1, reduce the production of inflammatory factors iNOS and COX-2, and reduce apoptosis via the endogenous apoptotic pathway. Taken together with previous studies on Gp (Shang et al 2006;Alhasani et al 2018;Yu et al 2016b;Yang et al 2017), we believe that this antioxidative effect may be directly associated with ROS clearance, improvement of endogenous antioxidant capacity, and reduced levels of inflammatory factors and mitochondrial damage, thereby reducing the rate of apoptosis. However, its specific mechanisms still require extensive study.…”

Section: Discussionsupporting

confidence: 78%

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

Zhang

Yuan

et al. 2020

J Mol Neurosci

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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.

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Section: Discussionsupporting

confidence: 78%

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

Zhang

Yuan

et al. 2020

J Mol Neurosci

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“…In the meantime, the mRNA expressions of Nrf2 and its target genes encoding phase II metabolizing enzymes and antioxidases (such as CAT, HO-1, SOD1, SOD2, GST-pi, NQO1, and GCLM) were also remarkably decreased by H 2 O 2 when compared with control cells ( Figure 5 ). These results are very similar to those of another group's work [ 59 ] in which they also used the high concentration (750 μ M) of H 2 O 2 to induce oxidative stressed model in ARPE-19 cells. Although, in the studies of another two groups who investigated the protective effects of apigenin [ 28 ] or quercetin [ 57 ] on tBHP or H 2 O 2 -induced oxidative stressed model in ARPE-19 cells, treatment with 200 μ M H 2 O 2 alone did not change the Nrf2 mRNA expression.…”

Section: Discussionsupporting

confidence: 90%

“…Numerous reports have proved that Nrf2 is an emerging regulator of cellular resistance to oxidative stress. Some natural products (such as apigenin, quercetin, gypenosides, genipin, rhizoma paridis, escin, and astaxanthin) have also been shown to have protective effects against the oxidative stressed ARPE-19 cells associated with Nrf2 signaling [28,[57][58][59][60][61][62][63]. In our study, we found that treatment with 1 mM H 2 O 2 for 24 h significantly induced a serious oxidative cell damage and apoptosis in ARPE-19 cells (Figures 1 and 2).…”

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confidence: 51%

Tribulus terrestris Ameliorates Oxidative Stress-Induced ARPE-19 Cell Injury through the PI3K/Akt-Nrf2 Signaling Pathway

Yuan

et al. 2020

Oxidative Medicine and Cellular Longevity

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Oxidative stress on retinal pigment epithelial (RPE) cells has been confirmed to play a crucial role in the development and progression of age-related macular degeneration (AMD) or other retinal degenerative diseases. Tribulus terrestris (TT) is a Chinese traditional herb medicine, which has been used for the treatment of ocular diseases for many centuries. In this study, we investigated the underlying mechanisms of TT and examined its ability to protect and restore the human retinal pigment epithelial cells (ARPE-19) against H2O2-induced oxidative stress. Our data show that 200 μg/mL of ethanol extract of Tribulus terrestris (EE-TT) significantly increased the cell viability and prevented the apoptosis of H2O2-treated ARPE-19 cells through the regulation of Bcl2, Bax, cleaved caspase-3, and caspase-9. Treatment with EE-TT also significantly decreased the upregulated reactive oxygen species (ROS) activities and increased the downregulated superoxide dismutase (SOD) activities induced by H2O2 in ARPE-19 cells. Additionally, H2O2 at 1 mM significantly decreased the mRNA expression levels of Nrf2, CAT, SOD1, SOD2, HO-1, GST-pi, NQO1, and GLCM in ARPE-19 cells; however, treatment with EE-TT reversed the downregulated mRNA expression levels of all these genes induced by H2O2. Furthermore, treatment with 200 μg/mL EE-TT alone for 24 h significantly increased Nrf2, HO-1, NQO1, and GCLM mRNA expressions in ARPE-19 cells when compared with untreated control cells. Pretreatment with the inhibitor of PI3K/Akt signaling (LY294002) completely blocked these EE-TT-upregulated mRNA expressions and abolished the improvement of cell viability in H2O2-treated ARPE-19 cells. These findings all suggest that Tribulus terrestris has significant antioxidant effects on oxidative stressed ARPE-19 cells through regulating PI3K/Akt-Nrf2 signaling pathway.

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“…Similar Nrf2 mediated protective effects against peroxide-induced toxicity have been reported in retinal epithelial cells (Alhasani et al, 2018). GYP treatment in a streptozotocin-induced diabetic rat model significantly upregulated Nrf2 expression and protected against oxidative stress (Gao et al, 2016).…”

Section: Effects Of Gyp On Protein Expression and Glp-1 Stainingsupporting

confidence: 71%

Effects of gypenosides on enteroendocrine L-cell function and GLP-1 secretion

Patibandla

Campbell

Shu

et al. 2020

Preprint

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Glucagon-like peptide 1 (GLP-1) is an incretin hormone produced in gut L-cells, which regulates postprandial glucose-dependent insulin secretion, also known as the incretin effect. GLP-1 secretion may be reduced in type 2 diabetes mellitus, impacting on glycaemic regulation. Thus, methods to enhance endogenous GLP-1 secretion by use of natural GLP-1 secretagogues may improve glucose control in diabetes. Gypenosides (GYP) extracted from the plant Gynostemma Pentaphyllum (Jiaogulan) are known for their glucose-lowering effects both in vitro and in vivo, although their effect on GLP-1 secretion is unknown. Our results showed that GYP enhanced cell viability and significantly upregulated antioxidant gene Nrf2, Cat and Ho-1 expression. GYP did not affect glucokinase expression but downregulated proglucagon gene expression over 24h, although, cellular GLP-1 content was unchanged. Prohormone convertase 1 (Pcsk1) gene expression was unchanged by GYP over 24h, although protein levels were significantly downregulated, while prohormone convertase 2 (Pcsk2) mRNA and protein levels were significantly upregulated. Acute exposure to gypenosides enhanced calcium uptake and GLP-1 release from GLUTag cells both at low and high glucose concentrations. These results suggest that anti-diabetic properties of gypenosides are partly linked to their ability to stimulate GLP-1 secretion. Gypenosides enhance antioxidant gene expression and may protect L-cells from excess oxidative stress.

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Gypenosides protect retinal pigment epithelium cells from oxidative stress

Cited by 36 publications

References 52 publications

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

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

Tribulus terrestris Ameliorates Oxidative Stress-Induced ARPE-19 Cell Injury through the PI3K/Akt-Nrf2 Signaling Pathway

Effects of gypenosides on enteroendocrine L-cell function and GLP-1 secretion

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