Goyal Ramesh K, Narwal Sonia, Bhatt Alok, Sehrawat Renu, Devi Pooja, Gulati Monica, Singla Rajeev K
Department of Pharmacology, School of Pharmaceutical Sciences, Delhi Pharmaceutical Sciences and Research University, New Delhi 110017, India.
Department of Pharmacy, Panipat Institute of Engineering and Technology, Samalkha, Panipat, Haryana 132101, India.
Curr Med Chem. 2024 May 30. doi: 10.2174/0109298673316493240527113707.
"Diabetes mellitus" is a chronic metabolic disorder manifested by elevated blood glucose levels, primarily due to insufficient insulin production or resistance to insulin. Long-term diabetes results in persistent complications like retinopathy, cardiomyopathy, nephropathy, and neuropathy, causing significant health risks. The most alarming microvascular consequence allied with diabetes is "diabetic retinopathy," distinguished by the proliferation of anomalous blood vessels in the eye, mainly in the retina, resulting in visual impairment, diabetic macular edema, and retinal detachment if left untreated. According to estimates, 27.0% of people with diabetes worldwide have retinopathy, which leads to 0.4 million blindness cases. It is believed that mitochondrial damage and the production of inflammatory mediators are the early indicators of diabetic retinopathy before any histological changes occur in the retina. Moreover, it is evident that augmented oxidative stress in the retina further initiates the NF-κB/MMP-9 downstream signaling pathway. Interestingly, these downstream regulators, Nuclear Factor Kappa B [NF- kB] and matrix metalloproteinases 9 [MMP-9], have been recognized as important regulators of the inception and advancement of diabetic retinopathy. This diabetes and oxidative stress-induced MMP-9 are believed to regulate various cellular functions, including angiogenesis and apoptosis, causing blood-retinal barrier breakdown and tight junction protein degradation that further leads to diabetic retinopathy. Thus, there is an emergency need for the treatment of diabetic retinopathy. Emerging treatment options include anti-VEGF, laser treatment, and eye surgery, but these have certain limitations. This comprehensive review explores the mechanisms of MMP-9 and NF-kB involvement in diabetic retinopathy and bioflavonoids' therapeutic potential and mechanisms of action in inhibiting MMP-9 activity and suppressing NF-kB-mediated inflammation. Clinical evidence supporting the use of bioflavonoids in mitigating diabetic complications and future perspectives are also examined.
“糖尿病”是一种慢性代谢紊乱疾病，主要表现为血糖水平升高，这主要是由于胰岛素分泌不足或对胰岛素产生抵抗所致。长期糖尿病会导致诸如视网膜病变、心肌病、肾病和神经病变等持续性并发症，带来重大健康风险。与糖尿病相关的最令人担忧的微血管后果是“糖尿病视网膜病变”，其特征是眼睛中，主要是视网膜中异常血管的增生，如果不治疗，会导致视力损害、糖尿病性黄斑水肿和视网膜脱离。据估计，全球27.0%的糖尿病患者患有视网膜病变，这导致了40万例失明病例。据信，线粒体损伤和炎症介质的产生是糖尿病视网膜病变的早期指标，此时视网膜尚未发生任何组织学变化。此外，很明显视网膜中氧化应激的增加会进一步启动NF-κB/MMP-9下游信号通路。有趣的是，这些下游调节因子，即核因子κB [NF-κB]和基质金属蛋白酶9 [MMP-9]，已被认为是糖尿病视网膜病变发生和发展的重要调节因子。这种由糖尿病和氧化应激诱导的MMP-9被认为可调节多种细胞功能，包括血管生成和细胞凋亡，导致血视网膜屏障破坏和紧密连接蛋白降解，进而导致糖尿病视网膜病变。因此，迫切需要治疗糖尿病视网膜病变。新兴的治疗选择包括抗血管内皮生长因子（VEGF）治疗、激光治疗和眼科手术，但这些都有一定的局限性。这篇综述探讨了MMP-9和NF-κB参与糖尿病视网膜病变的机制，以及生物类黄酮在抑制MMP-9活性和抑制NF-κB介导的炎症方面的治疗潜力和作用机制。还研究了支持使用生物类黄酮减轻糖尿病并发症的临床证据以及未来展望。
