Progress and perspective on hydrogen sulfide donors and their biomedical applications.

Following the discovery of nitric oxide (NO) and carbon monoxide (CO), hydrogen sulfide (H S) has been identified as the third gasotransmitter in humans. Increasing evidence have shown that H S is of preventive or therapeutic effects on diverse pathological complications. As a consequence, it is of great significance to develop suitable approaches of H S-based therapeutics for biomedical applications. H S-releasing agents (H S donors) play important roles in exploring and understanding the physiological functions of H S. More importantly, accumulating studies have validated the theranostic potential of H S donors in extensive repertoires of in vitro and in vivo disease models. Thus, it is imperative to summarize and update the literatures in this field. In this review, first, the background of H S on its chemical and biological aspects is concisely introduced. Second, the studies regarding the H S-releasing compounds are categorized and described, and accordingly, their H S-donating mechanisms, biological applications, and therapeutic values are also comprehensively delineated and discussed. Necessary comparisons between related H S donors are presented, and the drawbacks of many typical H S donors are analyzed and revealed. Finally, several critical challenges encountered in the development of multifunctional H S donors are discussed, and the direction of their future development as well as their biomedical applications is proposed. We expect that this review will reach extensive audiences across multiple disciplines and promote the innovation of H S biomedicine.