Oridonin protects hydrogen peroxide-induced human lens epithelial cell damage by regulating the NLRP3/NF-κB pathway and Nrf2-mediated oxidative stress

Jie Chen, Wei Zeng, Xili Xiao, Chen-Chen Lin
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Abstract

Cataract is the clouding of eye lens, and is the leading cause of visual impairment and blindness worldwide. There is an urgent need to develop new drugs to combat this disease. Oridonin (ORI), isolated from Rabdosia rubescens, is a natural substance that has been studied as an activator of nuclear factor erythroid 2-related factor 2 (Nrf2) and covalent inhibitor of NLR family pyrin domain containing 3 (NLRP3). Whether ORI has a therapeutic effect on human lens’ epithelial cell injury needs further study. In this study, we used cataract lens epithelial cell lines HLE-B3 and SRA01/04. We found using the MTT assay that ORI treatment increased cell viability induced by hydrogen peroxide (H2O2). In addition, ORI suppressed the apoptosis of H2O2-induced HLE-B3 and SRA01/04 cells detected by flow cytometry and Western blot analysis. Our data further revealed that ORI regulated nuclear factor, erythroid 2 (NFE2) like bZIP transcription factor 2 (Nrf2)-mediated oxidative stress by enzyme-linked-immunosorbent serologic assay. We further found that ORI inhibited NLRP3/nuclear factor-κb (NF-κB) pathway in H2O2-induced HLE-B3 and SRA01/04 cells by Western blot analysis. Therefore, these results suggested that ORI could have the potential to serve as a promising drug to treat cataract.
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Oridonin通过调节NLRP3/NF-κB通路和nrf2介导的氧化应激,保护过氧化氢诱导的人晶状体上皮细胞损伤
白内障是眼晶状体混浊,是世界范围内视力损害和失明的主要原因。迫切需要开发新药来对抗这种疾病。鸢尾草素(oriidonin, ORI)是一种天然物质,被研究为核因子红系2相关因子2 (Nrf2)的激活剂和NLR家族pyrin domain containing 3 (NLRP3)的共价抑制剂。ORI对人晶状体上皮细胞损伤是否有治疗作用有待进一步研究。本研究使用白内障晶状体上皮细胞系HLE-B3和SRA01/04。我们通过MTT实验发现,ORI处理增加了过氧化氢(H2O2)诱导的细胞活力。通过流式细胞术和Western blot检测,ORI可抑制h2o2诱导的HLE-B3和SRA01/04细胞的凋亡。我们的数据进一步通过酶联免疫吸附血清学分析显示ORI调节核因子,红细胞2 (NFE2)样bZIP转录因子2 (Nrf2)介导的氧化应激。Western blot分析进一步发现ORI对h2o2诱导的HLE-B3和SRA01/04细胞NLRP3/ NF -κb通路有抑制作用。因此,这些结果表明ORI有可能成为一种有前景的治疗白内障的药物。
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