Natural Molecules Targeting Thioredoxin System and Their Therapeutic Potential

Significance: 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. Recent Advance: 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. Critical Issues: 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 via interfering with the Trx system. Finally, we further discuss several natural molecules that harbor therapeutic potential and have entered different clinical trials. Future Directions: 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. Antioxid. Redox Signal. 34, 1083-1107.