Xie Ting, Chen Xiaodong, Chen Wenyi, Huang Sien, Peng Xinye, Tian Lingmei, Wu Xuejie, Huang Yan
Department of Ophthalmology and Optometry, Fujian Medical University, Fuzhou, China.
Medical Technology Experimental Teaching Center, Fujian Medical University, Fuzhou, China.
Front Pharmacol. 2021 Dec 10;12:796565. doi: 10.3389/fphar.2021.796565. eCollection 2021.
Curcumin is a natural polyphenol compound with anti-diabetic, anti-oxidative, and anti-inflammatory effects. Although many studies have reported the protective effect of curcumin in diabetes mellitus or diabetic nephropathy, there is a lack of research on curcumin in diabetic retinopathy. The purpose of this study was to investigate the therapeutic effects of curcumin on the diabetic retinal injury. Streptozotocin (STZ)-induced diabetic rats (60, = 12 each) were respectively given curcumin orally (200 mg/kg/day), insulin subcutaneously (4-6 IU/day), and combined therapy with curcumin and insulin for 4 weeks. Retinal histopathological changes, oxidative stress markers, and transcriptome profiles from each group were observed. Curcumin, insulin, or combination therapy significantly reduced blood glucose, alleviated oxidative stress, and improved pathological damage in diabetic rats. Curcumin not only significantly reduced retinal edema but also had a better anti-photoreceptor apoptosis effect than insulin. In the early stage of diabetes, the enhancement of oxidative stress in the retina induced the adaptive activation of the nuclear factor E2-associated factor 2 (Nrf2) pathway. Treatment of curcumin alleviated the compensatory activation of the Nrf2 pathway induced by oxidative stress, by virtue of its antioxidant ability to transfer hydrogen atoms to free radicals. When curcumin combined with insulin, the effect of maintaining Nrf2 pathway homeostasis in diabetic rats was better than that of insulin alone. Transcriptomic analyses revealed that curcumin either alone, or combined with insulin, inhibited the AGE-RAGE signaling pathway and the extracellular matrix (ECM)-receptor interaction in the diabetic retina. Thus, at the early stage of diabetes, curcumin can be used to alleviate diabetic retinal injury through its anti-oxidative effect. If taking curcumin as a potential complementary therapeutic option in combination with antihyperglycemic agents, which would lead to more effective therapeutic outcomes against diabetic complications.
姜黄素是一种具有抗糖尿病、抗氧化和抗炎作用的天然多酚化合物。尽管许多研究报道了姜黄素在糖尿病或糖尿病肾病中的保护作用，但关于姜黄素在糖尿病视网膜病变方面的研究较少。本研究旨在探讨姜黄素对糖尿病视网膜损伤的治疗作用。将链脲佐菌素（STZ）诱导的糖尿病大鼠（60只，每组12只）分别口服姜黄素（200毫克/千克/天）、皮下注射胰岛素（4 - 6国际单位/天）以及联合使用姜黄素和胰岛素治疗4周。观察每组大鼠的视网膜组织病理学变化、氧化应激标志物和转录组图谱。姜黄素、胰岛素或联合治疗均显著降低了血糖，减轻了氧化应激，并改善了糖尿病大鼠的病理损伤。姜黄素不仅显著减轻了视网膜水肿，而且在抗光感受器细胞凋亡方面比胰岛素具有更好的效果。在糖尿病早期，视网膜氧化应激的增强诱导了核因子E2相关因子2（Nrf2）通路的适应性激活。姜黄素治疗凭借其将氢原子转移到自由基的抗氧化能力，减轻了氧化应激诱导的Nrf2通路的代偿性激活。当姜黄素与胰岛素联合使用时，在糖尿病大鼠中维持Nrf2通路稳态的效果优于单独使用胰岛素。转录组分析表明，姜黄素单独使用或与胰岛素联合使用，均可抑制糖尿病视网膜中的晚期糖基化终末产物受体（AGE-RAGE）信号通路和细胞外基质（ECM）-受体相互作用。因此，在糖尿病早期，姜黄素可通过其抗氧化作用减轻糖尿病视网膜损伤。如果将姜黄素作为一种潜在的辅助治疗选择与降糖药物联合使用，可能会对糖尿病并发症产生更有效的治疗效果。
