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Background: Autism spectrum disorder (ASD) is heterogeneous neurodevelopmental disorders that primarily display social and communication impairments and restricted/repetitive behaviors. ASD prevalence has increased in recent years, yet very limited therapeutic targets and treatments are available to counteract the incapacitating disorder. Korean Red Ginseng (KRG) is a popular herbal plant in South Korea known for its wide range of therapeutic effects and nutritional benefits and has recently been gaining great scientific attention, particularly for its positive effects in the central nervous system. Objectives: Thus, in this study, we investigated the therapeutic potential of KRG in alleviating the neurobehavioral deficits found in the valproic acid (VPA)-exposed mice models of ASD. Design: Starting at 21 days old (P21), VPA-exposed mice were given daily oral administrations of KRG solution (100 or 200 mg/kg) until the termination of all experiments. From P28, mice behaviors were assessed in terms of social interaction capacity (P28-29), locomotor activity (P30), repetitive behaviors (P32), short-term spatial working memory (P34), motor coordination (P36), and seizure susceptibility (P38). Results: VPA-exposed mice showed sociability and social novelty preference deficits, hyperactivity, increased repetitive behavior, impaired spatial working memory, slightly affected motor coordination, and high seizure susceptibility. Remarkably, long-term KRG treatment in both dosages normalized all the ASD-related behaviors in VPA-exposed mice, except motor coordination ability. Conclusion: As a food and herbal supplement with various known benefits, KRG demonstrated its therapeutic potential in rescuing abnormal behaviors related to autism caused by prenatal environmental exposure to VPA.

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