Diosmetin attenuates oxidative stress-induced damage to lens epithelial cells via the mitogen-activated protein kinase (MAPK) pathway

Cataract is a global ophthalmic disease that blinds the eye, and oxidative stress is one of its primary causes. Apoptosis of lens epithelial cells (LECs) is considered the major cytological basis of many cataracts except congenital cataracts. The purpose of this study was to investigate whether diosmetin could reduce oxidative stress-induced damage to LECs, and explore its regulatory pathway. Lens epithelial cell line SRA01/04 was used as the object of study. Using ultraviolet B (UVB) and hydrogen peroxide (H2O2) as sources of oxidative stress, the protective effects of diosmetin at different concentrations on cells were investigated, including inhibition of proliferation, apoptosis, and oxidative stress. Molecular docking was then used to predict the target proteins and validation was performed at the cellular and protein levels. The oxidative stress of SRA01/04 was induced by UVB and H2O2, and inhibition of proliferation and apoptosis were observed. Here, diosmetin has a dose-dependent cell-protecting effect. This effect is achieved by targeting the MEK2 protein and inhibiting the MAPK signaling. In conclusion, diosmetin reduces H2O2- and UVB-induced inhibition of SRA01/04 proliferation and apoptosis by reducing oxidative stress-induced activation of the MAPK pathway.

白内障（Cataract）是一种可致盲的全球性眼科疾病，氧化应激（oxidative stress）是其主要致病诱因之一。除先天性白内障外，晶状体上皮细胞（lens epithelial cells, LECs）凋亡被认为是多数白内障发生的核心细胞学基础。本研究旨在探讨香叶木素（diosmetin）能否减轻氧化应激对晶状体上皮细胞造成的损伤，并阐明其调控通路。本研究以晶状体上皮细胞系SRA01/04为研究对象，采用紫外线B（ultraviolet B, UVB）与过氧化氢（hydrogen peroxide, H₂O₂）构建氧化应激模型，探究不同浓度香叶木素对细胞的保护作用，包括逆转细胞增殖抑制、减少细胞凋亡及缓解氧化应激的效果。随后通过分子对接（molecular docking）预测靶蛋白，并在细胞与蛋白水平开展验证实验。实验结果显示，UVB与H₂O₂可诱导SRA01/04细胞产生氧化应激，并引发细胞增殖抑制与凋亡；而香叶木素呈现出剂量依赖性的细胞保护效应。该保护作用通过靶向MEK2蛋白、抑制丝裂原活化蛋白激酶（mitogen-activated protein kinase, MAPK）信号通路得以实现。综上，香叶木素可通过抑制氧化应激介导的MAPK通路活化，减轻H₂O₂与UVB诱导的SRA01/04细胞增殖抑制与凋亡。