There exists a vast amount of evidence regarding the structural and functional changes that occur in the hippocampus, as well as the manifestation of autism spectrum disorder (ASD) phenotypes during childhood. Research studies have demonstrated that cloves possess a significant antioxidant capacity due to its phenolic compounds. These compounds exhibit remarkable protective properties against oxidative damage. Over the past few years, plasma technology has captured significant attention as a new approach due to its unique characteristics. On the other hand, biomedical studies have revealed that cold atmospheric plasma is a promising technology for the development of drug properties providing an effective biological effect. Thus, this research aimed at studying the effect of aqueous clove extract (ACE) and aqueous clove extract activated by plasma (ACEP) on cognitive impairment induced by oxidative stress. Methods and Materials: The bud’s activation via dielectric barrier discharge (DBD) procedure by exposing to N2 gas for 10 mins was conducted after grounding buds and passing by the sieve. In this experimental study, pregnant Wistar rats were divided into two control and experimental groups. In the experimental group, valproic acid (VPA) was injected intraperitoneally at a dose of 500 mg/kg on day 12/5 of pregnancy. 21 days after birth, 7 male pups were placed in each group. The control and the VPA group received saline, VPA + ACE group received ACE and the VPA + ACEP group received ACEP both orally at a dose of 15 mg/kg for 3 weeks. Finally, 42 days after birth, a novel object recognition test (NORT) was performed to evaluate short-term and long-term memory. The activity of superoxide dismutase (SOD) as an endogenous antioxidant enzyme was assessed by Genet method. Results: In the novel object recognition test, VPA injection significantly reduced the duration of interaction with the new object (p < 0.001) in the VPA group compared to the control. In compartment with clove extract, the experimental group treated with ACEP was able to significantly (p < 0.001) increase the interaction time with the novel object by improving memory while ACE administration showed no notably changes. We observed decreased in SOD activity in VPA compared to control (p < 0.05). While ACE treatment showed no remarkably changes compared to control, ACEP administration could significantly enhance SOD activity in compartment with VPA group (p < 0.01). Conclusion: The oral administration of clove which is rich in phenols can probably strengthen the learning process by improving oxidative damage involved in memory. Therefore, these results state that nitrogen-based CAP treatment is probably a positive and effective factor in developing bioactive herbal compounds by stimulating antioxidant features and enhancing memory improvements in the VPA rat model.
