Regulation of signaling pathways by metal and metal-doped nanozymes in inflammatory bowel disease: A therapeutic perspective

Abstract

Inflammatory bowel disease (IBD) is a chronic condition driven by oxidative stress and dysregulated immune responses. Key pathways like nuclear factor-kappa B (NF-κB) and Janus kinase/signal transducer and activator of transcription (JAK/STAT) play pivotal roles in IBD pathogenesis. By altering these pathways, pro-inflammatory cytokines including TNF-α, IL-6, and IL-1β are suppressed, lowering inflammation and re-establishing immunological balance. Novel treatments for IBD have been developed using metal-based nanozymes that are designed to replicate natural enzymatic processes. These nanozymes, including iron-doped, zinc-doped, ceria-doped, transition metal-doped, and noble metal-doped variants, exhibit robust catalytic activities, such as superoxide dismutase (SOD)-like, catalase (CAT)-like, and peroxidase (POD)-like functions. By scavenging reactive oxygen species (ROS) and restoring redox balance, they mitigate oxidative stress, a key driver of IBD progression. These nanozymes interact with important signaling pathways linked to IBD in addition to their enzymatic roles. They inhibit NF-κB signaling, reducing the release of pro-inflammatory cytokines, and regulate the JAK/STAT pathway to balance immunological responses. Their therapeutic potential is increased by this dual action, which concurrently addresses immunological dysregulation and oxidative stress. Metal-doped nanozymes are a promising substitute for conventional anti-inflammatory and immunosuppressive therapies due to their precise, targeted action. The review article explores the latest developments in metal based nanozyme research, their catalytic characteristics, and how they affect IBD treatment, as well as potential future paths for the area.