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利用天然产物靶向铁死亡治疗糖尿病及其并发症:机遇与挑战

Targeting Ferroptosis With Natural Products to Treat Diabetes and Its Complications: Opportunities and Challenges.

作者信息

Yu Hanyang, Fu Lu, Zhang Chen, Wang Shuguang, Song Jiaying, Zhu Yingying, Wang Furong

机构信息

College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, China.

Medicine College, Shandong University of Traditional Chinese Medicine, Jinan, China.

出版信息

Phytother Res. 2025 Jul 9. doi: 10.1002/ptr.70028.


DOI:10.1002/ptr.70028
PMID:40634143
Abstract

Diabetes mellitus (DM) is a common chronic metabolic disorder, and the recommended pharmacotherapies in DM guidelines can effectively alleviate symptoms of DM, but some drugs may have certain side effects. In contrast, natural products and their derivatives have shown promising therapeutic effects on DM with fewer side effects. Additionally, ferroptosis, as a form of cell death, is involved in the normal physiological and pathological regulation of the body. Numerous studies have demonstrated the crucial role of ferroptosis in the occurrence and progression of diabetes and its complications. Furthermore, there is evidence that natural compounds can play a role in the prevention and treatment of diabetes and its complications by inhibiting ferroptosis. This review aims to enhance the understanding of the role and iron death mechanism of natural compounds in the treatment of diabetes and its complications. It also emphasizes the significance of utilizing natural products for managing diabetes and its complications. We conducted a systematic literature search using PubMed, Web of Science, and Clinical Trials: The search used keywords including natural products, natural compounds, oxidative stress, diabetes mellitus, and diabetic kidney disease. Comprehensive research and compilation of existing literature were conducted. Ferroptosis is a newly discovered form of cell death that is caused by an excess of iron and the buildup of reactive oxygen species (ROS) and lipid peroxides (LPO). These factors can affect ferroptosis through various signaling pathways, including the system Xc/GSH/GPX4 axis, AMPK, and the E-cadherin-NF2-Hippo-YAP pathway. Additionally, p53 has been identified as a regulator of ferroptosis. In the development of type 2 diabetes mellitus (T2DM) and its complications, ferroptosis has been found to play a crucial role in numerous studies. These studies have also elucidated the specific pathways of ferroptosis in diabetes-related conditions such as diabetic cardiomyopathy (DCM), diabetic kidney disease (DKD), diabetic retinopathy (DR), diabetic peripheral neuropathy (DPN), and diabetic foot ulcers (DFU). Natural products have been widely used to treat diabetes and its complications, and some have been found to have inhibitory effects on ferroptosis. This article also provides a detailed overview of the toxicity, side effects, and current research progress of natural products in this context. Ferroptosis plays a crucial role in the development of T2DM and its associated complications, with multiple signaling pathways involved in its regulation. Natural compounds have been shown to have an impact on diabetes and its complications by inhibiting ferroptosis and regulating the associated signaling pathways. As such, natural products hold great potential for the treatment of diabetes and its complications.

摘要

糖尿病(DM)是一种常见的慢性代谢紊乱疾病,糖尿病指南中推荐的药物疗法可有效缓解糖尿病症状,但某些药物可能有一定副作用。相比之下,天然产物及其衍生物对糖尿病显示出有前景的治疗效果,且副作用较少。此外,铁死亡作为一种细胞死亡形式,参与机体正常的生理和病理调节。众多研究已证明铁死亡在糖尿病及其并发症的发生和发展中起关键作用。此外,有证据表明天然化合物可通过抑制铁死亡在糖尿病及其并发症的预防和治疗中发挥作用。本综述旨在加深对天然化合物在糖尿病及其并发症治疗中的作用和铁死亡机制的理解。它还强调了利用天然产物管理糖尿病及其并发症的重要性。我们使用PubMed、Web of Science和临床试验进行了系统的文献检索:检索使用的关键词包括天然产物、天然化合物、氧化应激、糖尿病和糖尿病肾病。对现有文献进行了全面的研究和汇编。铁死亡是一种新发现的细胞死亡形式,由铁过量以及活性氧(ROS)和脂质过氧化物(LPO)的积累引起。这些因素可通过多种信号通路影响铁死亡,包括系统Xc⁻/谷胱甘肽(GSH)/谷胱甘肽过氧化物酶4(GPX4)轴、腺苷酸活化蛋白激酶(AMPK)和E-钙黏蛋白-NF2-河马-Yes相关蛋白(YAP)通路。此外,p53已被确定为铁死亡的调节因子。在2型糖尿病(T2DM)及其并发症的发展过程中,众多研究发现铁死亡起关键作用。这些研究还阐明了铁死亡在糖尿病相关病症如糖尿病心肌病(DCM)、糖尿病肾病(DKD)、糖尿病视网膜病变(DR)、糖尿病周围神经病变(DPN)和糖尿病足溃疡(DFU)中的具体途径。天然产物已被广泛用于治疗糖尿病及其并发症,并且一些已被发现对铁死亡有抑制作用。本文还详细概述了在此背景下天然产物的毒性、副作用和当前研究进展。铁死亡在T2DM及其相关并发症的发展中起关键作用,其调节涉及多个信号通路。天然化合物已显示出通过抑制铁死亡和调节相关信号通路对糖尿病及其并发症产生影响。因此,天然产物在糖尿病及其并发症的治疗中具有巨大潜力。

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