Zuo Xiangrong, Wang Xiuxian, Xie Jing, Jia Yuhong
Department of Ophthalmology, Xingtai People's Hospital, No.818 Xiangdu North Road, Xingtai City, 054000, Hebei, China.
Int Ophthalmol. 2025 Apr 2;45(1):141. doi: 10.1007/s10792-025-03513-6.
Diabetic cataract (DC) is an ocular complication caused by diabetes. Currently, the main treatments for DC include pharmacological therapy and surgical intervention. The core objective of this study is to elucidate the specific mechanism of action of emodin in the treatment of DC, thereby providing potential targets for the treatment of DC.
CCK-8 kit was used to detect the effect of emodin on the activity of lens epithelial cells (LECs). The impact of emodin on the expression of inflammatory factors and apoptosis in high glucose-induced LECs were evaluated by utilizing ELISA and flow cytometry. Then, commercial kits were performed to detect the regulatory effects of emodin on oxidative stress and ferroptosis in high glucose LECs. The potential mechanism of emodin in combating DC by inhibiting ferroptosis was analyzed by network pharmacology methods, and protein binding activity to emodin was measured by molecular docking. Besides, western blot (WB) assay was used to detect the effect of emodin on p53.
Firstly, the results of CCK-8 showed that emodin could effectively alleviate the decrease of LECs cell activity and Lactate dehydrogenase (LDH) release induced by high glucose. Emodin suppressed high glucose-induced apoptosis of LECs, reduced the release of inflammatory factors, and alleviated oxidative stress and ferroptosis. GO and KEGG analyses confirmed the involvement of oxidative stress (OS), inflammatory response, and ferroptosis in the process of emodin treatment for DC. Molecular docking studies showed that emodin stably bound to proteins such as TP53, TNF, IL-6, and IL-1β. Additionally, WB results indicated that emodin alleviated high glucose-induced ferroptosis by binding to p53.
Collectively, these data suggest that emodin alleviates damage to LECs by interfering with the p53-mediated ferroptosis pathway, thereby attenuating DC disease, which offered new directions for the development of new drugs.
糖尿病性白内障（DC）是糖尿病引起的一种眼部并发症。目前，DC的主要治疗方法包括药物治疗和手术干预。本研究的核心目的是阐明大黄素治疗DC的具体作用机制，从而为DC的治疗提供潜在靶点。
采用CCK-8试剂盒检测大黄素对晶状体上皮细胞（LEC）活性的影响。利用ELISA和流式细胞术评估大黄素对高糖诱导的LEC中炎症因子表达和细胞凋亡的影响。然后，使用商业试剂盒检测大黄素对高糖LEC中氧化应激和铁死亡的调节作用。通过网络药理学方法分析大黄素通过抑制铁死亡对抗DC的潜在机制，并通过分子对接测量蛋白与大黄素的结合活性。此外，采用蛋白质免疫印迹（WB）分析检测大黄素对p53的影响。
首先，CCK-8结果显示大黄素可有效缓解高糖诱导的LEC细胞活性降低和乳酸脱氢酶（LDH）释放。大黄素抑制高糖诱导的LEC细胞凋亡，减少炎症因子释放，减轻氧化应激和铁死亡。基因本体（GO）和京都基因与基因组百科全书（KEGG）分析证实氧化应激（OS）、炎症反应和铁死亡参与了大黄素治疗DC的过程。分子对接研究表明大黄素与TP53、TNF、IL-6和IL-1β等蛋白稳定结合。此外，WB结果表明大黄素通过与p53结合减轻高糖诱导的铁死亡。
总体而言，这些数据表明大黄素通过干扰p53介导的铁死亡途径减轻对LEC的损伤，从而减轻DC病情，这为新药开发提供了新方向。
