背景:呼吸系统疾病对人类生命构成严重威胁。因此,了解其发病机制和治疗策略很重要。Ferroptosis是一种新型的铁依赖性程序性细胞死亡,与细胞凋亡不同,坏死,和自噬,以铁为特征,活性氧,和脂质过氧化物积累,以及谷胱甘肽(GSH)消耗和GSH过氧化物酶4(GPX4)失活。铁死亡与呼吸系统疾病的发生和发展密切相关,包括慢性阻塞性肺疾病,急性肺损伤,支气管哮喘,肺纤维化,肺癌,已被报道。最近的研究表明,中药(TCM)化合物由于其天然性质和潜在的功效,在治疗呼吸系统疾病方面表现出独特的优势。这些化合物可以通过调节几个关键的信号通路,如系统Xc-GSH-GPX4,NCOA4介导的铁蛋白吞噬,Nrf2-GPX4和Nrf2/HO-1,从而在改善呼吸系统疾病方面发挥积极作用。
目的:本综述系统概述了铁性凋亡在呼吸系统疾病发生发展中的调节作用,为中药复方靶向铁性凋亡治疗呼吸系统疾病提供依据。这些见解旨在为呼吸道疾病的临床预防和治疗提供潜在的补救措施。
方法:我们搜索了科学数据库PubMed,WebofScience,Scopus,和CNKI使用“Ferroptosis”等关键词,“呼吸系统疾病”,“慢性阻塞性肺疾病”,“支气管哮喘”,“急性肺损伤”,“肺纤维化”,“肺癌”,“中药”,“中药复方”,“单体”,和“天然产物”,以检索中药复方通过靶向铁性凋亡改善呼吸系统疾病的治疗潜力的研究。检索到的数据遵循PRISMA标准(系统审查的首选报告项目)。
结果:中药复方在治疗呼吸系统疾病方面具有独特的优势,源于它们的自然起源和证明的临床有效性。中药复方可以通过调节铁性凋亡对呼吸系统疾病发挥治疗作用,这主要涉及通路的调节,如系统Xc-GSH-GPX4,NCOA4介导的铁蛋白吞噬,Nrf2-GPX4和Nrf2/HO-1。
结论:中药复方在通过调节铁凋亡改善呼吸系统疾病方面具有良好的潜力。确定特定的中药相关铁死亡诱导剂和抑制剂对于制定更有效的策略具有重要意义。然而,目前的研究仍然局限于动物和细胞研究,强调通过高质量临床数据进行进一步验证的必要性。
BACKGROUND: Respiratory diseases pose a grave threat to human life. Therefore, understanding their pathogenesis and therapeutic strategy is important. Ferroptosis is a novel type of iron-dependent programmed cell death, distinct from apoptosis, necroptosis, and autophagy, characterised by iron, reactive oxygen species, and lipid peroxide accumulation, as well as glutathione (GSH) depletion and GSH peroxidase 4 (GPX4) inactivation. A close association between ferroptosis and the onset and progression of respiratory diseases, including chronic obstructive pulmonary disease, acute lung injury, bronchial asthma, pulmonary fibrosis, and lung cancer, has been reported. Recent studies have shown that traditional Chinese medicine (TCM) compounds exhibit unique advantages in the treatment of respiratory diseases owing to their natural properties and potential efficacy. These compounds can effectively regulate ferroptosis by modulating several key signalling pathways such as system Xc- -GSH-GPX4, NCOA4-mediated ferritinophagy, Nrf2-GPX4, and Nrf2/HO-1, thus playing a positive role in improving respiratory diseases.
OBJECTIVE: This comprehensive review systematically outlines the regulatory role of ferroptosis in the onset and progression of respiratory diseases and provides evidence for treating respiratory diseases by targeting ferroptosis with TCM compounds. These insights aim to offer potential remedies for the clinical prevention and treatment of respiratory diseases.
METHODS: We searched scientific databases PubMed, Web of Science, Scopus, and CNKI using keywords such as \"ferroptosis\",\"respiratory diseases\",\"chronic obstructive pulmonary disease\",\"bronchial asthma\",\"acute lung injury\",\"pulmonary fibrosis\",\"lung cancer\",\"traditional Chinese medicine\",\"traditional Chinese medicine compound\",\"monomer\", and \"natural product\" to retrieve studies on the therapeutic potential of TCM compounds in ameliorating respiratory diseases by targeting ferroptosis. The retrieved data followed PRISMA criteria (preferred reporting items for systematic review).
RESULTS: TCM compounds possess unique advantages in treating respiratory diseases, stemming from their natural origins and proven clinical effectiveness. TCM compounds can exert therapeutic effects on respiratory diseases by regulating ferroptosis, which mainly involves modulation of pathways such as system Xc- -GSH-GPX4,NCOA4-mediated ferritinophagy, Nrf2-GPX4, and Nrf2/HO-1.
CONCLUSIONS: TCM compounds have demonstrated promising potential in improving respiratory diseases through the regulation of ferroptosis. The identification of specific TCM-related inducers and inhibitors of ferroptosis holds great significance in developing more effective strategies. However, current research remains confined to animal and cellular studies, emphasizing the imperative for further verifications through high-quality clinical data.