Astragaloside IV protects retinal pigment epithelial cells from apoptosis by upregulating miR‑128 expression in diabetic rats

Wang, Tao; Zhang, Zhongwei; Song, Caiping; Sun, Lei; Sui, Xinli; Qun, QU; Liu, Jing

doi:10.3892/ijmm.2020.4588

Cited by 21 publications

(13 citation statements)

References 30 publications

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“…Therefore, it is of great significance to explore the pathogenesis of DR and develop new therapeutic methods to improve the prognosis of DR. In this study, PC was found to have a protective effect on RPE under high glucose, presented by increased cell viability, decreased apoptosis rate and reduced expression of Bax and Caspase‐3 and increased expression of Bcl‐2, the commonly used apoptosis markers, 16,17 of ARPE‐19 cells treated with PC. Our results were similar to other studies on anthocyanidins, which can be produced from PC when heated in acidic medium, in the protection of visual function and diabetes 18…”

Section: Discussionmentioning

confidence: 72%

Procyanidin protects human retinal pigment epithelial cells from high glucose by inhibiting autophagy

Zhang

2021

Environmental Toxicology

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Purpose The damage of hyperglycemia to the retinal pigment epithelial (RPE) cells is a critical event in diabetic retinopathy (DR). Procyanidin (PC), a kind of polyphenol compounds, has shown to be effective in preventing and treating diabetes as well as its complications, in which autophagy disorder is involved in the pathological mechanism. However, it remains unclear whether PC can play a protective role in DR by regulating the autophagy of RPE. Here, the effect of PC on RPE under high glucose conditions and the role of autophagy were investigated. Materials and Methods The cell viability of ARPE‐19, a human RPE cell line, was detected by cell counting kit‐8 (CCK‐8) and the apoptosis rate was measured by flow cytometry. The protein expressions of apoptosis markers, including Bax, Bcl‐2, and Caspase‐3, as well as autophagy markers including LC3, p62, p53, and mTOR were detected by Western blotting. Autophagic flux in ARPE‐19 cells was detected by transfection with Ad‐mCherry‐GFP‐LC3B. Results Under high glucose conditions, the viability of ARPE‐19 was decreased and the apoptosis rate increased, the protein expressions of Bax, Caspase‐3, LC3‐II/LC3‐I, and p‐p53 were all increased and the expressions of Bcl‐2, p62, and p‐mTOR decreased, and autophagic flux was increased compared with that of the controls. Treatment with PC weakened all these changes caused by high glucose. When rapamycin (RPM), an autophagy agonist was added, the cell viability of ARPE‐19 by PC treatment was decreased while the apoptosis was increased. Conclusions Our findings indicate that through the p53/mTOR autophagy pathway, PC may protect RPE cells from high glucose‐induced injury.

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Section: Discussionmentioning

confidence: 72%

Procyanidin protects human retinal pigment epithelial cells from high glucose by inhibiting autophagy

Zhang

2021

Environmental Toxicology

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“…Emerging evidences have shown that 6-OHDA can induce apoptosis and promote the levels of apoptotic proteins such as Bax ( Wang T. et al, 2020 ). Hence, we explored the role of AS-IV in the apoptosis of 6-OHDA-treated SH-SY5Y cells.…”

Section: Resultsmentioning

confidence: 99%

Astragaloside IV Protects 6-Hydroxydopamine-Induced SH-SY5Y Cell Model of Parkinson’s Disease via Activating the JAK2/STAT3 Pathway

Xu¹,

Yang²,

Huang³

et al. 2021

Front. Neurosci.

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ObjectivesAstragaloside IV (AS-IV), the main active component of Astragalus membranaceus, bears anti-inflammatory, antioxidant, and neuroprotective activity. Parkinson’s disease (PD) is a common neurodegenerative disease. This study explored the protective effect of AS-IV on the cell model of PD.Materials and MethodsSH-SY5Y cells were incubated with different concentrations (10, 50, 100, 150, and 200 μM) of 6-hydroxydopamine (6-OHDA) for 0, 3, 6, 12, 24, and 48 h to establish the PD cell model. Different concentrations (0, 25, 50, 100, 150, and 200 μM) of AS-IV or 15 mM JAK2/STAT3 pathway inhibitor SC99 was added for intervention 2 h before 6-OHDA treatment. The viability and morphological damage of 6-OHDA-treated SH-SY5Y cells were measured using MTT assay and Hoechst 33258 staining. The expression of microtubule associated protein 2 (MAP2) was detected by immunofluorescence staining. The levels of inflammation and oxidative stress were measured using ELISA. Apoptosis of 6-OHDA-treated SH-SY5Y cells was detected using flow cytometry, and phosphorylation level of JAK2 and STAT3 were detected using Western blot analysis.ResultsThe survival rate of SH-SY5Y cells treated with 100 μM 6-OHDA for 24 h was about 50%. AS-IV (25–100 μM) significantly improved the viability (all p < 0.01), increased MAP2 expression, and repaired the morphological damage induced by 6-OHDA. AS-IV inhibited IL-1β, IL-6, and TNF-α level (all p < 0.05), reduced MDA and ROS content and increased SOD concentration, thereby reducing inflammation and oxidative stress (all p < 0.01) in 6-OHDA-treated SH-SY5Y cells. Moreover, AS-IV decreased apoptosis rate and Bax/Bcl-2 ratio induced by 6-OHDA (all p < 0.05). Mechanically, AS-IV significantly increased the phosphorylation of JAK2 and STAT3 (p < 0.01); the addition of SC99 decreased the cell viability, increased the apoptosis rate, enhanced the levels of inflammatory factors and oxidative stress.ConclusionAS-IV enhanced the cell viability, and inhibited apoptosis, inflammation and oxidative stress of 6-OHDA-treated SH-SY5Y cells via activating the JAK2/STAT3 signaling pathway. This study may confer novel insights for the management of PD.

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“…AS-IV, a high-purity natural product extracted from A. membranaceus , has remarkable antioxidant activity. In previous studies with RPE cells, AS-IV was shown to inhibit expression of miR-128 and the TRAF5 signaling pathway, thereby reducing the level of apoptosis induced by high glucose and isoflurane [ 16 , 38 ]. In adriamycin-induced cardiomyopathy, AS-IV inhibited ferroptosis, thereby inhibiting myocardial fibrosis and cardiac dysfunction [ 39 ].…”

Section: Discussionmentioning

confidence: 99%

“…Thus, AS-IV seems to effectively mitigate the pathological process leading to DR [ 14 , 15 ]. Importantly, AS-IV has been shown to effectively inhibit death of RPE cells during streptozocin-induced DR; changes occurring at cellular level showed that AS-IV can inhibit cell damage induced by high glucose levels by increasing the expression of miR-128 [ 16 ]. Therefore, it would of interest to determine whether AS-IV can mitigate damage to RPE cells by inhibiting ferroptosis.…”

Section: Introductionmentioning

confidence: 99%

Astragaloside-IV alleviates high glucose-induced ferroptosis in retinal pigment epithelial cells by disrupting the expression of miR-138-5p/Sirt1/Nrf2

Tang

Zhang

et al. 2022

Bioengineered

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Astragaloside-IV (AS-IV) (C 41 H 68 O 14 ) is a high-purity natural product extracted from Astragalus , which has demonstrated biological activities. However, the effect of AS-IV on retinal pigment epithelial (RPE) cells in diabetic retinopathy (DR) remains unclear. In this study, high glucose (HG) was shown to promote ARPE-19 RPE cell death, increase the contents of reactive oxygen species (ROS) and oxidized glutathione (GSSG), and enhance lipid peroxidation density of mitochondrial membrane. In contrast, AS-IV decreased glutathione (GSH) content, mitochondria size and ridge. Addition of iron death inhibitor Ferrostatin-1 (Fer-1) to RPE cells decreased cell dead rate, thus indicating that HG-induced mitochondrial damage occurred due to ferroptosis. AS-IV alleviated HG-induced RPE cell damage. Furthermore, HG decreased levels of silent information regulator 1 (Sirt1) and nuclear factor (erythroid-derived 2)-like 2 (Nrf2) in the nucleus of RPE cells; AS-IV could alleviate these effects and increased expression of glutathione peroxidase 4 (GPX4), glutamate cysteine ligase (GCLM) and glutamate cysteine ligase catalytic subunit (GCLC), which are Nrf2 downstream genes. Mechanistically, AS-IV was shown to alleviate the effects of HG by increasing mir-138-5p expression in RPE cells and promoting expression of Sirt1 and Nrf2 in the nucleus. Transfection of mir-138-5p agonist inhibited the regulatory effects of AS-IV on Sirt1 and Nrf2, accompanied by decreased GPX4, GCLM and GCLC levels, and restoration of ferroptosis-related changes. Collectively, HG increased ferroptosis rate in RPE cells. In addition, AS-IV inhibited miR-138-5p expression, subsequently increasing Sirt1/Nrf2 activity and cellular antioxidant capacity to alleviate ferroptosis, resulting decreased cell death, which potentially inhibits the DR pathological process.

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Astragaloside IV protects retinal pigment epithelial cells from apoptosis by upregulating miR‑128 expression in diabetic rats

Cited by 21 publications

References 30 publications

Procyanidin protects human retinal pigment epithelial cells from high glucose by inhibiting autophagy

Procyanidin protects human retinal pigment epithelial cells from high glucose by inhibiting autophagy

Astragaloside IV Protects 6-Hydroxydopamine-Induced SH-SY5Y Cell Model of Parkinson’s Disease via Activating the JAK2/STAT3 Pathway

Astragaloside-IV alleviates high glucose-induced ferroptosis in retinal pigment epithelial cells by disrupting the expression of miR-138-5p/Sirt1/Nrf2

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