Abstract
Depression constitutes a significant global social issue. Numerous therapeutic medications have been developed in accordance with the monoamine hypothesis；nonetheless, the prevalence of treatment-resistant depression remains a pressing clinical concern. Hence, it is imperative to contemplate an alternative approach that extends beyond the confines of monoamine systems. Recently, substantial attention has been directed toward the gut-brain axis, a concept suggesting that the intestinal environment influences brain function. Nevertheless, the intricate mechanism associated with the gut-brain axis remain incompletely elucidated. In this study, our specific focus resides on intestinal reactive oxygen species（ROS）, as elevated ROS levels are known to disturb the intestinal environment. To investigate the impact of scavenging intestinal ROS on depression treatment via the gut-brain axis, a novel polymer-based antioxidant（siSMAPoTN） was purposefully engineered for exclusive distribution within the intestinal tract following oral administration. siSMAPoTN was designed to selectively scavenge intestinal ROS and protected the intestinal environment from harm induced by chronic restraint stress（CRS）. In addition, the administration of siSMAPoTN resulted in the suppression of physiological and behavioral symptoms associated with depression in the CRS mouse model.
