Arbutin as a therapeutic candidate for autism: Current evidence and mechanistic insights into PI3K/Akt/mTOR and Nrf2 pathways.

Arbutin is a natural glycoside that protects neurons and is useful in a variety of neurological conditions. There is a need to further explore its scientific properties as arbutin regulates mitochondrial function, control apoptotic proteins, lowers oxidative stress, enhance behavioral and cognitive outcomes and thus may be considered a potential target for Parkinson's, Alzheimer's, neuroinflammation, epilepsy and Huntington's disease. Arbutin via PI3K/Akt/mTOR and Nrf2 signaling pathways, helps to balance redox equilibrium, mitochondrial integrity and neuronal survival, plays a major role in mediating these effects. Autism Spectrum Disorder (ASD) is closely associated with dysfunction of these pathways, which cause oxidative 2 stress, synaptic deficits and neuroinflammation. While reducing NF-κB mediated pro-inflammatory cytokines including TNF-α, IL-1β and IL-6, arbutin increases Akt phosphorylation and Nrf2 nuclear translocation, activating antioxidant enzymes like SOD, GSH, HO-1 and NQO1. These coordinated molecular processes may help preserve neuronal homeostasis, inhibit apoptosis and decrease ROS induced neuronal damage. Arbutin may enhance synaptic plasticity and potentially modulate the pathogenic pathways underlying ASD and other neurodevelopmental disorders by concurrently regulating oxidative stress, mitochondrial dysfunction and neuroinflammation. Taken together these finding suggest arbutin may act as a promising therapeutic candidate capable of restoring neuronal homeostasis and translating mechanistic understanding into potential therapeutic applications. Arbutin is a promising phytochemical with potential relevance for autism and associated neurological diseases due to its combined molecular actions. However, direct experiment and clinical evidence supporting the role of arbutin in ASD remains limited.