Baicalin suppresses glaucoma pathogenesis by regulating the PI3K/AKT signaling in vitro and in vivo

Zhao, Na; Shi, Jieran; Xu, Hao; Luo, Qing; Li, Qiaoyan; Liu, Mingzhou

doi:10.1080/21655979.2021.2001217

Cited by 20 publications

(12 citation statements)

References 45 publications

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“…The PI3K/Akt signaling pathway participates in regulation of antioxidant functions in RPE cells [ 39–41 ]. and retinal ganglion cells [ 42 ]. It is reported that the activation of Akt protects RPE cells from oxidant-mediated cell death under normal conditions and diseases, including AMD [ 43 ].…”

Section: Discussionmentioning

confidence: 99%

Recombinant human klotho protects against hydrogen peroxide-mediated injury in human retinal pigment epithelial cells via the PI3K/Akt-Nrf2/HO-1 signaling pathway

Wen

Zhang

et al. 2022

Bioengineered

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Globally, age-related macular degeneration (AMD) is a common irreversible ophthalmopathy. Oxidative stress of retinal pigment epithelial cells is involved in AMD occurrence and development. Klotho is an anti-aging protein with antioxidant properties. We investigated the protective properties of Klotho on hydrogen peroxide (H 2 O 2 )-induced injury of retinal pigment epithelial cells (ARPE-19 cells) and its associated pathomechanisms. We found that Klotho pretreatment for 24 h could up-regulate Bcl-2 levels, decrease the cleaved-caspase-3 and Bax levels, inhibit H 2 O 2 -induced ARPE-19 cell apoptosis, and promote cell proliferation. Klotho pretreatment inhibited the H 2 O 2 -mediated elevations of reactive oxygen species (ROS) in ARPE-19 cells. It enhanced antioxidant activities of the cells and restored the glutathione peroxidase (GPX), superoxide dismutase (SOD2), catalase (CAT), as well as malondialdehyde (MDA) levels to close to the normal level. N-acetylcysteine (NAC), a reactive oxygen scavenger, could reverse the harmful effects of H 2 O 2 on proliferation, apoptosis, and oxidative stress of ARPE-19 cells. Further, Klotho pretreatment enhanced Akt phosphorylation and expression as well as nuclear translocation of Nrf2 in H 2 O 2 -treated ARPE-19 cells. This indicates that Klotho protects cells from oxidative stress by activating phosphatidylinositol 3 kinase (PI3K)/protein kinase B (Akt)-nuclear factor E2-related factor 2 (Nrf2)/heme oxygenase 1 (HO-1) signaling pathway. Klotho is, therefore, a potential preventive or treatment option for AMD.

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Section: Discussionmentioning

confidence: 99%

Recombinant human klotho protects against hydrogen peroxide-mediated injury in human retinal pigment epithelial cells via the PI3K/Akt-Nrf2/HO-1 signaling pathway

Wen

Zhang

et al. 2022

Bioengineered

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“…The disease can be effectively slowed down by interfering with the functions of human retinal pigment cells. For example, sulforaphane ameliorates amyloid-β-induced injury in RPE cells ( 15 ), recombinant human klotho protects against hydrogen peroxide-mediated injury in human retinal pigment epithelial cells ( 16 ), and baicalin suppresses AMD in vitro and in vivo ( 17 ). In AMD, functional changes in the RPE play an important role; neovascularization is particularly important, and its occurrence is closely related to the proliferation and activity of vascular endothelial cells.…”

Section: Introductionmentioning

confidence: 99%

Regulator of G-protein signaling 1 promotes choroidal neovascularization in age-related macular degeneration

Zhang¹,

Zhang²,

Guo³

et al. 2022

Ann Transl Med

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Background: Age-related macular degeneration (AMD) is the leading cause of blindness, and is associated with oxidative stress and the development of new blood vessels. At present, the main clinical treatment for AMD includes intraocular injection of vascular endothelial growth factor (VEGF). However, treatment includes repeated injections with significant side-effects. Therefore, new treatment options are required. The aim of the present study was to discover the new treatment target of AMD from the gene level. Methods: The Gene Expression Omnibus (GEO) database was used to analyze the differential gene expression in AMD, and the regulator of G-protein signaling 1 (RGS1) was obtained by bioassay. Western blotting and quantitative reverse transcription polymerase chain reaction (qRT-PCR) were used to detect the expression levels of RGS1, VEGF, and other related molecules in human microvascular endothelial cells (HMECs) under different conditions. Cell viability, apoptosis, and proliferation of HMECs were measured by Cell Counting Kit-8 proliferation assay. Immunofluorescence and immunohistochemistry detected the interaction between RGS1, platelet endothelial cell adhesion molecule-1, and VEGF. Results: RGS1 was found to closely associated with the proliferation of vascular endothelial cells, and therefore, with angiogenesis. The expression of RGS1, VEGF, and platelet endothelial cell adhesion molecule-1 was upregulated in laser model mice and hypoxia model HMECs. Knockout of RGS1 inhibits the expression of VEGF and HMEC proliferation, thereby inhibiting AMD angiogenesis. Conclusions: Our results support the use of RGS1 as a new potential target for the future treatment of AMD.

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“…Plant flavonoid supplementation is being studied for the treatment for a range of different ocular disorders (31). For example, baicalein has been found to lower intraocular pressure in glaucoma (32) by regulating PI3K/AKT signalling (33), while quercetin provides neuroprotective effects in diabetic rat retinas (34) and in mouse models of light-induced retinal degeneration (35).…”

Section: Discussionmentioning

confidence: 99%

Eupatilin improves cilia defects in human CEP290 ciliopathy models

Corral-Serrano¹,

Sladen²,

Ottaviani

et al. 2023

Preprint

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The photoreceptor outer segment is a highly specialized primary cilium essential for phototransduction and vision. Biallelic pathogenic variants in the cilia-associated gene CEP290 cause non-syndromic Leber congenital amaurosis 10 (LCA10) and syndromic diseases, where the retina is also affected. While RNA antisense oligonucleotides and gene editing are potential treatment options for the common deep intronic variant c.2991+1655A>G in CEP290, there is a need for variant-independent approaches that could be applied to a broader spectrum of ciliopathies. Here, we generated several distinct human models of CEP290-related retinal disease and investigated the effects of the flavonoid eupatilin as a potential treatment. Eupatilin improved cilium formation and length in CEP290 LCA10 patient-derived fibroblasts, in gene-edited CEP290 knockout (CEP290 KO) RPE1 cells, and in both CEP290 LCA10 and CEP290 KO iPSCs-derived retinal organoids. Furthermore, eupatilin reduced rhodopsin retention in the outer nuclear layer of CEP290 LCA10 retinal organoids. Eupatilin altered gene transcription in retinal organoids, by modulating the expression of rhodopsin, and by targeting cilia and synaptic plasticity pathways. This work sheds light into the mechanism of action of eupatilin, and supports its potential as a variant-independent approach for CEP290-associated ciliopathies.

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Baicalin suppresses glaucoma pathogenesis by regulating the PI3K/AKT signaling in vitro and in vivo

Cited by 20 publications

References 45 publications

Recombinant human klotho protects against hydrogen peroxide-mediated injury in human retinal pigment epithelial cells via the PI3K/Akt-Nrf2/HO-1 signaling pathway

Recombinant human klotho protects against hydrogen peroxide-mediated injury in human retinal pigment epithelial cells via the PI3K/Akt-Nrf2/HO-1 signaling pathway

Regulator of G-protein signaling 1 promotes choroidal neovascularization in age-related macular degeneration

Eupatilin improves cilia defects in human CEP290 ciliopathy models

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