Targeting the AGE-RAGE axis in acute lung injury: Mechanistic insights and redox-modulatory strategies

Acute Respiratory Distress Syndrome (ARDS) is a serious respiratory condition characterized by a rapid onset of severe inflammation in the lungs. This inflammation results from various causes. The syndrome is marked by widespread damage to the alveolar epithelial cells and capillary endothelial cells. It represents a critical stage of acute lung injury (ALI), a prevalent clinical issue associated with a high mortality rate. The underlying mechanisms of ALI are intricate and primarily driven by an uncontrolled inflammatory response. Given this complexity, there has been growing interest recently in the role of advanced glycation end-products (AGEs) and their receptor, the receptor for advanced glycation end-products (RAGE), in the development of ALI. The AGE-RAGE signaling pathway is pivotal in the initiation and progression of ALI, influencing several processes, including inflammation and apoptosis. However, the detailed mechanisms by which this signaling pathway contributes to ALI are still being investigated. This review aims to summarize recent advancements in understanding the molecular mechanisms, regulation of inflammatory responses, and apoptosis associated with the AGE-RAGE signaling pathway in ALI. It focuses on analyzing how various traditional Chinese medicine formulas and their active components can modulate this pathway to alleviate ALI. Additionally, by integrating network pharmacology, molecular docking, and experimental validation, this review examines the interactions between the AGE-RAGE signaling pathway and significant downstream pathways such as NF-κB and PI3K/AKT, highlighting their potential therapeutic implications. Therefore, this work provides a foundational understanding of the pathogenesis of ALI and paves the way for the development of innovative therapeutic approaches.