State Key Laboratory of Applied Organic Chemistry, College of Chemistry and Chemical Engineering, and School of Pharmacy, Lanzhou University, Lanzhou, China.
Shaanxi Key Laboratory of Phytochemistry, Baoji University of Arts and Sciences, Baoji, China.
Antioxid Redox Signal. 2021 May 10;34(14):1083-1107. doi: 10.1089/ars.2020.8213. Epub 2020 Dec 4.
Thioredoxin (Trx) and thioredoxin reductase are two core members of the Trx system. The system bridges the gap between the universal reducing equivalent NADPH and various biological molecules and plays an essential role in maintaining cellular redox homeostasis and regulating multiple cellular redox signaling pathways. In recent years, the Trx system has been well documented as an important regulator of many diseases, especially tumorigenesis. Thus, the development of potential therapeutic molecules targeting the system is of great significance for disease treatment. We herein first discuss the physiological functions of the Trx system and the role that the Trx system plays in various diseases. Then, we focus on the introduction of natural small molecules with potential therapeutic applications, especially the anticancer activity, and review their mechanisms of pharmacological actions interfering with the Trx system. Finally, we further discuss several natural molecules that harbor therapeutic potential and have entered different clinical trials. Further studies on the functions of the Trx system in multiple diseases will not only improve our understanding of the pathogenesis of many human disorders but also help develop novel therapeutic strategies against these diseases. 34, 1083-1107.
硫氧还蛋白（Trx）和硫氧还蛋白还原酶是 Trx 系统的两个核心成员。该系统连接了普遍的还原当量 NADPH 和各种生物分子之间的桥梁，在维持细胞氧化还原稳态和调节多种细胞氧化还原信号通路方面发挥着重要作用。近年来，Trx 系统已被充分证明是许多疾病，特别是肿瘤发生的重要调节剂。因此，开发针对该系统的潜在治疗性分子对于疾病治疗具有重要意义。 我们首先讨论了 Trx 系统的生理功能以及该系统在各种疾病中的作用。然后，我们重点介绍了具有潜在治疗应用的天然小分子，特别是其抗癌活性，并综述了它们通过干扰 Trx 系统发挥药理作用的机制。最后，我们进一步讨论了几种具有治疗潜力并已进入不同临床试验阶段的天然分子。 进一步研究 Trx 系统在多种疾病中的功能不仅将提高我们对许多人类疾病发病机制的理解，而且有助于开发针对这些疾病的新型治疗策略。34, 1083-1107.
