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硝基二氢辣椒素,一种非辣味辣椒素类似物,通过上调 SIRT1 抑制晶状体上皮细胞的细胞衰老。

Nitro Dihydrocapsaicin, a Non-Pungent Capsaicin Analogue, Inhibits Cellular Senescence of Lens Epithelial Cells via Upregulation of SIRT1.

机构信息

Department of Optometry, Faculty of Allied Health Sciences, Naresuan University, Phitsanulok 65000, Thailand.

Department of Chemistry, Faculty of Science, Naresuan University, Phitsanulok 65000, Thailand.

出版信息

Int J Mol Sci. 2022 Nov 12;23(22):13960. doi: 10.3390/ijms232213960.

Abstract

Diabetic cataracts are a common complication that can cause blindness among patients with diabetes mellitus. A novel nitro dihydrocapsaicin (NDHC), a capsaicin analog, was constructed to have a non-pungency effect. The objective of this research was to study the effect of NDHC on human lens epithelial (HLE) cells that lost function from hyperglycemia. HLE cells were pretreated with NDHC before an exposure to high glucose (HG) conditions. The results show that NDHC promoted a deacceleration of cellular senescence in HLE cells. This inhibition of cellular senescence was characterized by a delayed cell growth and lower production of reactive oxygen species (ROS) as well as decreased SA-β-galactosidase activity. Additionally, the expression of Sirt1 protein sharply increased, while the expression of p21 and phospho-p38 proteins decreased. These findings provide evidence that NDHC could exert a pharmacologically protective effect by inhibiting the senescence program of lens cells during diabetic cataracts.

摘要

糖尿病性白内障是糖尿病患者常见的并发症,可导致失明。一种新型的硝基二氢辣椒素(NDHC),一种辣椒素类似物,被构建为具有非刺激性作用。本研究的目的是研究 NDHC 对高血糖引起的人晶状体上皮(HLE)细胞功能丧失的影响。HLE 细胞在暴露于高葡萄糖(HG)条件之前用 NDHC 预处理。结果表明,NDHC 促进了 HLE 细胞的细胞衰老减速。这种细胞衰老的抑制作用表现为细胞生长延迟,活性氧(ROS)产生减少,SA-β-半乳糖苷酶活性降低。此外,Sirt1 蛋白的表达急剧增加,而 p21 和磷酸化 p38 蛋白的表达减少。这些发现提供了证据,表明 NDHC 通过抑制糖尿病性白内障期间晶状体细胞的衰老程序,发挥药理学保护作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/04ab/9695757/392bab8b5dda/ijms-23-13960-g001.jpg

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