Department of Medical Laboratory Sciences, College of Applied Medical Sciences, University of Hail, 2440, Saudi Arabia.
Department of Biosciences, Integral University, Lucknow 226026, India.
Int J Biol Macromol. 2024 Nov;280(Pt 2):135761. doi: 10.1016/j.ijbiomac.2024.135761. Epub 2024 Sep 19.
Diabetes mellitus significantly increases mortality and morbidity rates due to complications like neuropathy and nephropathy. It also leads to retinopathy and cataract formation, which is a leading cause of vision disability. The polyol pathway emerges as a promising therapeutic target among the various pathways associated with diabetic complications. This review focuses on the development of natural and synthetic aldose reductase inhibitors (ARIs), along with recent discoveries in diabetic complication treatment. AR, pivotal in the polyol pathway converting glucose to sorbitol, plays a key role in secondary diabetes complications' pathophysiology. Understanding AR's function and structure lays the groundwork for improving ARIs to mitigate diabetic complications. New developments in ARIs open up exciting possibilities for treating diabetes-related complications. However, it is still challenging to get preclinical successes to clinical effectiveness because of things like differences in how the disease starts, drug specificity, and the complexity of the AR's structure. Addressing these challenges is crucial for developing targeted and efficient ARIs. Continued research into AR's structural features and specific ARIs is essential. Overcoming these challenges could revolutionize diabetic complication treatment, enhance patient outcomes, and reduce the global burden of diabetes-related mortality and morbidity.
糖尿病会导致神经病变和肾病等并发症，从而显著增加死亡率和发病率。它还会导致视网膜病变和白内障的形成，这是导致视力残疾的主要原因。多元醇途径在与糖尿病并发症相关的各种途径中脱颖而出，成为一个有前途的治疗靶点。本综述重点介绍了天然和合成醛糖还原酶抑制剂（ARIs）的发展，以及在糖尿病并发症治疗方面的最新发现。醛糖还原酶（AR）在多元醇途径中将葡萄糖转化为山梨醇中起着关键作用，在继发性糖尿病并发症的病理生理学中起着关键作用。了解 AR 的功能和结构为改善 ARIs 以减轻糖尿病并发症奠定了基础。ARIs 的新进展为治疗与糖尿病相关的并发症开辟了令人兴奋的可能性。然而，由于疾病起始方式、药物特异性和 AR 结构的复杂性等因素，将临床前的成功转化为临床效果仍然具有挑战性。解决这些挑战对于开发有针对性和有效的 ARIs 至关重要。继续研究 AR 的结构特征和特定的 ARIs 至关重要。克服这些挑战可能会彻底改变糖尿病并发症的治疗方式，改善患者的治疗效果，并降低与糖尿病相关的死亡率和发病率的全球负担。
