BIOMEDICINE & PHARMACOTHERAPY
·
2023
·
IF 7.5
Zhangnian Liu,Shiquan Gan,Lingyun Fu,Yini Xu,Shengquan Wang,Guangqiong Zhang,Di Pan,Ling Tao,Xiangchun Shen
1,8-Cineole, the main component of volatile oil in aromatic plants, has diverse pharmacological properties, including antioxidant, anti-inflammatory, and anti-cancer properties. Diabetic retinopathy (DR) is a common microvascular complication of diabetes mellitus (DM). Here, we investigated the protective effect of 1,8-cineole on DR and found that 1,8-cineole treatment could alter the expression of several genes in both high glucose (HG)-induced ARPE-19 cells and retinal tissues of DM mice, as well as inhibit ferroptosis. Subsequent investigations into the molecular mechanisms underlying this inhibition revealed that expression of thioredoxin-interacting protein (TXNIP) was significantly upregulated while that of peroxisome proliferator-activated receptor γ (PPAR-γ) was significantly downregulated in HG-induced ARPE-19 cells, and treatment with 1,8-cineole could effectively reverse these changes. Treatment with a PPAR-γ pharmacological agonist (rosiglitazone), alone or combined with 1,8-cineole, significantly inhibited the transcription of TXNIP and ferroptosis in HG-induced ARPE-19 cells. Conversely, pretreatment with GW9662, a PPAR-γ inhibitor, upregulated the transcription and expression of TXNIP in HG-induced ARPE-19 cells; 1,8-cineole failed to reverse this upregulated expression. To explore these relationships, we constructed a PPAR-γ adenovirus shRNA to elucidate the effect of 1,8-cineole on the negative regulation of TXNIP by PPAR-γ. Taken together, the present findings indicate that HG-induced ferroptosis in retinal tissue plays an essential role in the pathogenesis of DR, which can be ameliorated by 1,8-cineole.
研究领域:
药理学
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眼科学
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分子生物学
·
糖尿病研究
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产品关联
DOI
PubMed
高影响因子
EXPERIMENTAL EYE RESEARCH
·
2015
·
IF 2.709
Yang Bian,Luqing Ren,Lei Wang,Shanmei Xu,Jianjian Tao,Xiuhua Zhang,Yi Huang,Yuanyuan Qian,Xin Zhang,Zongming Song,Wencan Wu,Yi Wang,Guang Liang
Inflammation is a pathological hallmark of ischemia reperfusion (I/R) injury. The present study was conducted to explore the ability of a new anti-inflammatory compound, X22, to attenuate retinal I/R injury via cytokine-inhibitory mechanism. For the in vitro experiment, ARPE-19 cells were pretreated with X22 (5 or 10 μM) or saline for 2 h, followed by stimulation with tert-butyl hydroperoxide (TBHP, 1000 μM) for an indicated amount of time. The expression of inflammatory mediators , cell viability , and cell apoptosis were evaluated. For the in vivo experiment, the rats were randomized to receive treatment with saline or X22 (0.1 μM/kg, 3 μL) before the induction of I/R injury. Histological evaluation, apoptosis of retinal cells, macrophage infiltration, and retina functional changes were further determined. Our data showed that pretreatment with X22 significantly inhibited TBHP-induced inflammatory cytokine expression in ARPE-19 cells. The anti-inflammatory activity of X22 may be associated with its inhibition on MAPKs, rather than NF-κB. Subsequently, our data proved that TBHP induced apoptosis in ARPE-19 cells, while pretreatment of X22 significantly suppressed TBHP-caused ARPE-19 apoptosis. Finally, the in vivo data revealed that X22 administration maintained better inner retinal layer structures, reduced apoptosis of retinal ganglion cell, and improved retinal function in retinal I/R rat models, which were accompanied with a remarkable decrease in retinal macrophage infiltration. These results suggest that the novel compound X22 is a potential agent for the treatment of retinal I/R-related diseases via the MAPKs-targeting anti-inflammatory mechanism and deserves the further development.
研究领域:
眼科学
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药理学
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炎症研究
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神经保护
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DOI
PubMed
高影响因子
Journal of Functional Foods
·
2024
·
IF 3.8
Xi-you Li,Xiao-yuan Gu,Bai-ling Zhou,Bun Tsoi,Wei-xi Li
Eye deformity, a noteworthy embryopathy, is intricately linked with maternal diabetes, frequently resulting in embryonic malformation or even death. In this investigation, a hyperglycemic chick embryo model was established to delve into the protective potential of tamarind shell extract (TSE) on eye development. Chick embryos were administered with TSE (at dosages of 1, 2, and 4 µg/egg) through air sac injection on embryo development day 0 (EDD0) and later exposed to D-glucose (0.4 mmol/egg) on EDD1. To validate our findings, we replicated hyperglycemic environment using D-glucose in ARPE-19 cell model. Our research unveiled that TSE proficiently counters O-GlcNAcylation of proteins in the presence of D-glucose, thereby reinstating levels of key proteins involved in eye development, including Pax6, Daam1, mTOR, and Cdc42. Furthermore, TSE was pinpointed to curtail the D-glucose concentration within the embryo eye, considerably decreasing the accumulation of reactive oxygen species and malondialdehyde accumulation in both the ARPE-19 cells and chick embryos. Beyond its fundamental role in boosting the cellular antioxidative activity, the improved expression of apoptosis-related proteins like Caspase-3, BAX, BCL-2 and other like PI3K and AKT were observed. This suggests a probable activation of the PI3K-AKT-mTOR pathway on ARPE-19 cells by TSE, thereby downregulating apoptotic proteins in ARPE-19 cells during oxidative stress. TSE may become a potent natural countermeasure against D-glucose-induced eye malformation.
研究领域:
发育生物学
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药理学
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细胞生物学
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胚胎学
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产品关联
DOI
高影响因子
Food & Function
·
2021
·Vol. 12
·期 16
·7198-7213
·
IF 5.396
Xinyao Liu,Fei Zheng,Sheng Li,Zhitong Wang,Xinyuan Wang,Liankui Wen,Yang He
Malvidin (MV) and its derivatives, such as malvidin-3-O-guaiacol (Mv3C) and malvidin-3-O-6-(acrylic acid-(2-hydroxy,4-carboxy-cyclohexanol)ester)-guaiacol (Mv3ACEC), are natural compounds with antioxidant properties. However, the basic mechanisms underlying their functional activities are unclear. In this study, we show that MV, Mv3C, and Mv3ACEC inhibit reactive oxygen species production and malondialdehyde content, promote glutathione peroxidase activity, and increase superoxide dismutase levels in ARPE-19 cells treated with H2O2. Western blotting and immunofluorescence analysis revealed that MV, Mv3C, and Mv3ACEC regulate mitogen-activated protein kinase signal transduction pathways related to endoplasmic reticulum stress. Interestingly, Mv3C and Mv3ACEC showed greater beneficial properties than MV. Our results show that MV and its derivatives have potential as therapeutic compounds for ocular diseases associated with oxidative stress, such as age-related macular degeneration.
研究领域:
药理学
·
细胞生物学
·
眼科
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产品关联
DOI
PubMed
高影响因子
Biomaterials Science
·
2022
·Vol. 11
·期 1
·278-287
·
IF 7.59
Xiulin Cheng,Panjing Yin,Ting Li,Lincong Luo,Yang Yang,Ling Wang,Weiwei Su,Yilin Wang,Yanbing Li,Yanfang Wang,Yaobin Wu,Wenhua Huang
Retinal pigment epithelial (RPE) cell transplantation is being explored as a feasible approach for treating age-related macular degeneration. The low aggregation ability of RPE cell suspensions or microtissues after transplantation has limited cell utilisation. Therefore, alternative transplantation strategies should be explored to induce cell aggregation and maintain cell viability. Herein, we propose a composite hydrogel that encapsulates gelatin methacryloyl (GelMA)/chitosan microspheres (GCMSs) as ARPE-19 cell transplantation carriers. The diameter of the GCMS was adjusted by tuning the parameters of the microfluidic devices, yielding a cell-adhering platform that induced uniform cell spreading. The live/dead assay and immunofluorescence results showed that ARPE-19 cells adhered and spread uniformly around the microspheres. Moreover, the hydrogel sheets were used to provide an aggregated protective shell, and the ARPE-19 cells on the microspheres encapsulated within these hydrogel sheets remained viable post-injection and produced fewer reactive oxygen species after cyclic stretching. Furthermore, we found that the composite hydrogel was biodegradable and biocompatible in vivo. Therefore, GCMSs provide an injectable microcarrier for ARPE-19 cells, and the hydrogel provides an aggregated protective shell in this novel platform, which has considerable potential for an alternative injectable and highly aggregated RPE cell transplantation strategy design.
研究领域:
生物材料
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组织工程
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眼科学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
CELL STRESS & CHAPERONES
·
2020
·Vol. 26
·期 2
·367-375
·
IF 2.892
Chen Jun,Li Lihua,Zhou Yun,Zhang Jiahua,Chen Lei
Diabetic retinopathy (DR) is a serious microvascular complication of diabetes. Gambogic acid has been reported to have anti-inflammatory effect. However, the effect of GA on inflammatory response of ARPE-19 cells remains unclear. In our study, ARPE-19 cells were stimulated by palmitic acid (PA) induction in the presence of 30 mM glucose and then treated with 0.5, 1, 2, 5, 10, or 20 μM GA. CCK-8 assay showed that cell viability was increased by GA treatment at doses of 0.5, 1, and 2 μM instead of higher doses. ELISA analysis found that GA dose-dependently reduced the production of pro-inflammatory mediators TNF-α and IL-1β. Western blot indicated that GA downregulated the expression of NLRP3 inflammasome components including TXNIP, NLRP3, ASC, cleaved-caspase-1, and cleaved-IL-1β in a dose-dependent manner. In addition, Western blot and immunofluorescence analysis suggested that GA effectively increased the protein level of nuclear factor E2-related factor-2 (Nrf2). RT-qPCR showed that GA significantly increased the mRNA levels of Heme oxygenase-1 (HO-1) and NADPH:quinone oxidoreductase1 (NQO1). Furthermore, Nrf2 siRNA transfection confirmed the above effects of GA. In total, subtoxic doses of GA significantly flattened the inflammatory response induced by HG and PA in ARPE-19 cells via modulating the Nrf2 signaling pathway.
研究领域:
药理学
·
细胞生物学
·
糖尿病研究
·
炎症
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产品关联
DOI
PubMed
高影响因子
CELLULAR SIGNALLING
·
2021
·
IF 4.315
Hao Huang,Xielan Kuang,Xiaobo Zhu,Hao Cheng,Yuxiu Zou,Han Du,Han Tang,Linbin Zhou,Jingshu Zeng,Huijun Liu,Jianhua Yan,Chongde Long,Huangxuan Shen
Retinal ischemia-reperfusion (I/R) often results in intractable visual impairments, where blood retinal barrier (BRB) homeostasis mediated by retinal pigment epithelium (RPE) and retinal microvascular endothelium (RME) is crucial. However, strategies targeting the BRB are limited. Thus, we investigated the inconclusive effect of lycopene (LYC) in retinal protection under I/R. LYC elevated cellular viability and reversed oxidative stress in aRPE-19 cells/hRME cells under I/R conditions based on oxygen-glucose deprivation (OGD) in vitro . Molecular analysis showed that LYC promoted NRF2 expression and enhanced the downstream factors of the KEAP1/NRF2/ARE pathway: LYC increased the activities of antioxidants, including SOD and CAT , whereas it enhanced the mRNA expression of HO-1 ( ho-1 ) and NQO-1 ( nqo-1 ). The activation resulted in restrained ROS and MDA. On the other hand, LYC ameliorated the damage to retinal function and morphology in a mouse I/R model, which was established by unilateral ligation of the left pterygopalatine artery/external carotid artery and reperfusion . LYC promoted the expression of NRF2 in both the neural retina and the RPE choroid in vivo . This evidence revealed the potential of LYC in retinal protection under I/R, uncovering the pharmacological effect of the KEAP1/NRF2/ARE pathway in BRB targeting. The study generates new insights into scientific practices in retinal research.
研究领域:
眼科学
·
药理学
·
分子生物学
·
细胞生物学
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产品关联
DOI
PubMed
高影响因子
TOXICOLOGY AND APPLIED PHARMACOLOGY
·
2020
·
IF 3.347
Qiongtao Song,Ying Zhao,Yanrong Yang,Xue Han,Junguo Duan
Iron overload toxicity has been implicated in retinal pigment epithelial cell injury in age-related macular degeneration. This study investigates the effects of astragaloside IV (AS-IV), a potential retinal protective agent, on the toxicity process of retinal iron overload in vivo and in vitro . AS-IV partially restored the retinal expression of rhodopsin and retinal pigment epithelium-specific 65 kDa protein, suppressed oxidative stress and inflammatory markers, and alleviated iron deposition and retinal pathological changes in vivo . Also, AS-IV inhibited the phosphorylation of p38 and ERK mitogen-activated protein kinases (MAPKs), as well as the nuclear translocation of nuclear factor-kappa B (NF-κB). Furthermore, AS-IV prevented cell death by decreasing the ratio of Bax/Bcl-2, caspase-3, and cleaved caspase-3 expression in vitro . Although there are no chelation effects between AS-IV and iron, AS-IV can reduce intracellular iron by regulating iron-handling proteins in ARPE-19 cells (Cav1.2, divalent metal transporter-1, transferrin receptor 1 , and heavy-chain ferritin). In conclusion, the results show that AS-IV has significant protective effects against retinal iron overload toxicity and suggest that iron regulation and the inhibition of MAPKs and NF-κB activation might be mechanisms underlying the effects of AS-IV.
研究领域:
眼科学
·
药理学
·
分子生物学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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