Dihydromyricetin alleviates attention deficit hyperactivity disorder by modulating the SIRT1/Nrf2/Keap1/HO-1 signaling pathway

Attention deficit hyperactivity disorder (ADHD) is a prevalent neurodevelopmental disorder characterized by inattention, hyperactivity, and impulsivity, with limited effective treatments available. This study investigated the therapeutic potential of Dihydromyricetin (DMY) in a monosodium glutamate (MSG)-induced ADHD mouse model. Behavioral tests, including open field, Y-maze, and social interaction tests, were conducted to assess hyperactivity, attention, and social behavior. Molecular mechanisms were evaluated through Western blot analysis of oxidative stress markers (MDA, GPx, MPO) and key signaling proteins (SIRT1, Keap1, Nrf2, HO-1), as well as ELISA measurement of inflammatory cytokines (NF-κB, IL-6, TNF-α, IL-1β). Histological analysis assessed neuronal damage in the hippocampus and prefrontal cortex. Results showed that DMY treatment significantly improved ADHD-like behaviors, including reduced hyperactivity and enhanced attention and social interaction. It also restored oxidative balance by downregulating MPO, GPx and MDA levels. DMY modulated the SIRT1/Nrf2/Keap1/HO-1 pathway, attenuating inflammation and neuronal damage. These findings suggest that DMY alleviates ADHD symptoms by reducing oxidative stress and inflammation, highlighting its potential as a novel therapeutic agent for ADHD.