Physiological forgetting is an essential process for normal brain function, yet the molecular mechanisms underlying memory loss, including pathologically accelerated forms, are still not fully elucidated. A key mechanism to induce forgetting was identified in Caenorhabditis elegans (C. elegans) involving the RNA-binding protein Musashi (MSI), which acts as a translational regulator. Here, we report the discovery of a series of nanomolar inhibitors of MSI identified via a high-throughput natural product screening platform of a plant extract library. Ellagic acid (EA) emerged as one of the most potent inhibitors, improving both short- and long-term associative memory in an all-or-none like manner in an in vivo C. elegans memory model. Notably, EA had no effect in msi loss-of-function mutant worms, corroborating MSI as its molecular target. These findings underscore MSI as a therapeutic target for modulating forgetting and establish EA as a nanomolar MSI inhibitor and promising lead compound for mitigating memory decay. Read more