Dihydroquercetin Nanomicelles Mitigate Hippocampal Apoptosis and Alleviate Autism-Like Behaviors in ASD Rats via the IKK/IKB/NF-κB Signaling Pathway

Dihydroquercetin (DHQ), a compound with neuroprotective effects, has shown its potential in a variety of nervous system diseases. However, its mechanism of action in autism spectrum disorder (ASD) remains to be further explored. Due to its poor solubility, the clinical application of DHQ is restricted. In this study, we aimed to improve the solubility of DHQ by constructing a novel nanodrug delivery system. We utilized the amphiphilic block copolymer MANNOSE-PEG2000-DSPE to encapsulate DHQ, and the resulting formulation was abbreviated as MAN@DHQ. The ASD rats were treated with MAN@DHQ for 7 days. The results of in vivo experiments confirmed that MAN@DHQ could effectively alleviate autism-like behaviors of ASD rats. Western blot results demonstrated that MAN@DHQ mitigate hippocampal apoptosis and ameliorated neuronal damage in the hippocampus of ASD rats via the IKK/IKB/NF-κB signaling pathway. The therapeutic potential of MAN@DHQ in ASD treatment represents a paradigm-shifting advancement in autism pharmacotherapy and offers promise for clinical interventions for ASD patients.