Fucoxanthin mitigates valproic acid-induced autistic behavior through modulation of the AKT/GSK-3β signaling pathway

Abstract

This study aimed to investigate the effects of fucoxanthin, a natural compound found in seaweed, on various aspects of autism using a rat model induced by valproic acid (VPA). Pregnant rats were administered VPA (600 mg/kg) on gestational day 12.5, and male pups were orally administered fucoxanthin at 50, 100, or 200 mg/kg beginning on post-natal day (PND) 23–43. Behavioral assessments were conducted on PND 45–53, and on PND 54, the animals were sacrificed for further biochemical analyses (superoxide dismutase (SOD) and glutathione (GSH), nitric oxide (NO)) via UV spectroscopy. Inflammatory markers (IL-17, TNF-α, and IL-1β) were also analyzed by sandwich ELISA, and the molecular parameters were evaluated through ELISA. The results revealed that, compared with VPA, fucoxanthin improved behavior and neuronal morphology. Specifically, fucoxanthin administration was found to enhance spatial memory, reduce pain sensitivity, and improve social interaction, locomotor activity, balance, and motor coordination. Fucoxanthin also exhibited anti-inflammatory and antioxidant effects, as indicated by the restoration of SOD and GSH levels and reduced inflammatory cytokine levels. Molecular analyses revealed that fucoxanthin restored the levels of GSK-3β and AKT. Furthermore, fucoxanthin regulates neurotransmitters, which are related to increasing GABA and reducing glutamate levels in the cortex and cerebellum. The therapeutic effects were dose-dependent, with higher doses (200 mg/kg) showing greater efficacy than lower doses (100 mg/kg) in improving behavioral, biochemical, neurotransmitter, and molecular parameters. Fucoxanthin is a potential treatment for autism, but further research, including clinical trials, is necessary to determine its effectiveness in humans.