Institute of Medical Sciences, Tzu Chi University, Hualien 970, Taiwan.
Department of Molecular Biology and Human Genetics, Tzu Chi University, Hualien 970, Taiwan.
Mar Drugs. 2020 Dec 23;19(1):1. doi: 10.3390/md19010001.
Age-related macular degeneration (AMD) is a progressive eye disease that causes irreversible impairment of central vision, and effective treatment is not yet available. Extracellular accumulation of amyloid-beta (Aβ) in drusen that lie under the retinal pigment epithelium (RPE) has been reported as one of the early signs of AMD and was found in more than 60% of Alzheimer's disease (AD) patients. Extracellular deposition of Aβ can induce the expression of inflammatory cytokines such as IL-1β, TNF-α, COX-2, and iNOS in RPE cells. Thus, finding a compound that can effectively reduce the inflammatory response may help the treatment of AMD. In this research, we investigated the anti-inflammatory effect of the coral-derived compound 4-(phenylsulfanyl) butan-2-one (4-PSB-2) on Aβ oligomer (oAβ) added to the human adult retinal pigment epithelial cell line (ARPE-19). Our results demonstrated that 4-PSB-2 can decrease the elevated expressions of TNF-α, COX-2, and iNOS via NF-κB signaling in ARPE-19 cells treated with oAβ without causing any cytotoxicity or notable side effects. This study suggests that 4-PSB-2 is a promising drug candidate for attenuation of AMD.
年龄相关性黄斑变性（AMD）是一种进行性眼病，可导致中心视力不可逆转的损害，目前尚无有效的治疗方法。在视网膜色素上皮（RPE）下的 沉积物中，细胞外淀粉样β（Aβ）的积累被报道为 AMD 的早期标志之一，在超过 60%的阿尔茨海默病（AD）患者中发现了这种情况。Aβ 的细胞外沉积可诱导 RPE 细胞中炎症细胞因子如 IL-1β、TNF-α、COX-2 和 iNOS 的表达。因此，寻找一种能有效降低炎症反应的化合物可能有助于 AMD 的治疗。在这项研究中，我们研究了珊瑚衍生的化合物 4-（苯硫基）-2-丁酮（4-PSB-2）对加入人成年视网膜色素上皮细胞系（ARPE-19）的 Aβ 寡聚物（oAβ）的抗炎作用。我们的结果表明，4-PSB-2 可通过 NF-κB 信号通路降低 oAβ 处理的 ARPE-19 细胞中 TNF-α、COX-2 和 iNOS 的升高表达，而不会引起任何细胞毒性或明显的副作用。这项研究表明，4-PSB-2 是一种有前途的药物候选物，可用于减轻 AMD。
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