Triptonide protects retinal cells from oxidative damage via activation of Nrf2 signaling.

IF 8.3 2区 材料科学 Q1 MATERIALS SCIENCE, MULTIDISCIPLINARY ACS Applied Materials & Interfaces Pub Date : 2024-09-01 Epub Date: 2024-07-12 DOI:10.3892/ijmm.2024.5400
Jinjing Li, Jiajun Li, Yuan Cao, Jin Yuan, Yaming Shen, Linyi Lei, Keran Li
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Abstract

Age‑related macular degeneration (AMD) is an ocular disease that threatens the visual function of older adults worldwide. Key pathological processes involved in AMD include oxidative stress, inflammation and choroidal vascular dysfunction. Retinal pigment epithelial cells and Müller cells are most susceptible to oxidative stress. Traditional herbal medicines are increasingly being investigated in the field of personalized medicine in ophthalmology. Triptonide (Tn) is a diterpene tricyclic oxide, the main active ingredient in the extract from the Chinese herbal medicinal plant Tripterygium wilfordii, and is considered an effective immunosuppressant and anti‑inflammatory drug. The present study investigated the potential beneficial role of Tn in retinal oxidative damage in order to achieve personalized treatment for early AMD. An oxidative stress model of retinal cells induced by H2O2 and a retinal injury model of mice induced by light and N‑Methyl‑D‑aspartic acid were constructed. In vitro, JC‑1 staining, flow cytometry and apoptosis assay confirmed that low concentrations of Tn effectively protected retinal cells from oxidative damage, and reverse transcription‑quantitative PCR and western blotting analyses revealed that Tn reduced the expression of retinal oxidative stress‑related genes and inflammatory factors, which may depend on the PI3K/AKT/mTOR‑induced Nrf2 signaling pathway. In vivo, by retinal immunohistochemistry, hematoxylin and eosin staining and electroretinogram assay, it was found that retinal function and structure improved and choroidal neovascularization was significantly inhibited after Tn pretreatment. These results suggested that Tn is an efficient Nrf2 activator, which can be expected to become a new intervention for diseases such as AMD, to inhibit retinal oxidative stress damage and pathological neovascularization.

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曲普奈德通过激活 Nrf2 信号来保护视网膜细胞免受氧化损伤。
老年性黄斑变性(AMD)是一种威胁全球老年人视觉功能的眼部疾病。老年黄斑变性的主要病理过程包括氧化应激、炎症和脉络膜血管功能障碍。视网膜色素上皮细胞和 Müller 细胞最容易受到氧化应激的影响。在眼科个性化医疗领域,对传统草药的研究日益增多。雷公藤内酯(Tn)是一种二萜三环氧化物,是中药植物雷公藤提取物的主要活性成分,被认为是一种有效的免疫抑制剂和抗炎药物。本研究调查了 Tn 在视网膜氧化损伤中的潜在有益作用,以实现早期 AMD 的个性化治疗。本研究构建了由 H2O2 诱导的视网膜细胞氧化应激模型以及由光和 N-甲基-D-天冬氨酸诱导的小鼠视网膜损伤模型。在体外,JC-1染色、流式细胞术和细胞凋亡检测证实,低浓度Tn能有效保护视网膜细胞免受氧化损伤,逆转录-定量PCR和Western印迹分析表明,Tn能降低视网膜氧化应激相关基因和炎症因子的表达,这可能依赖于PI3K/AKT/mTOR诱导的Nrf2信号通路。在体内,通过视网膜免疫组化、苏木精和伊红染色以及视网膜电图检测发现,Tn预处理后视网膜功能和结构得到改善,脉络膜新生血管明显受到抑制。这些结果表明,Tn是一种高效的Nrf2激活剂,有望成为治疗AMD等疾病的一种新的干预手段,以抑制视网膜氧化应激损伤和病理性新生血管形成。
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来源期刊
ACS Applied Materials & Interfaces
ACS Applied Materials & Interfaces 工程技术-材料科学:综合
CiteScore
16.00
自引率
6.30%
发文量
4978
审稿时长
1.8 months
期刊介绍: ACS Applied Materials & Interfaces is a leading interdisciplinary journal that brings together chemists, engineers, physicists, and biologists to explore the development and utilization of newly-discovered materials and interfacial processes for specific applications. Our journal has experienced remarkable growth since its establishment in 2009, both in terms of the number of articles published and the impact of the research showcased. We are proud to foster a truly global community, with the majority of published articles originating from outside the United States, reflecting the rapid growth of applied research worldwide.
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