Attenuative Effect of Zingerone on Behavioural Anomalies and Oxidative Stress in The Cerebellum of Prenatal Valproic Acid Induced Autism Spectrum Disorder Like Symptoms in F1 Female Pups: In Vivo Modelling

Abstract The pilot study aimed to evaluate the attenuative effect of zingerone (ZNO) against valproic acid (VPA)-induced autism spectrum disorder (ASD) like symptoms in the cerebellum of female rat pups. Pregnant female rats were administered with VPA (500mg/Kg/i.p) as a single dose on the 12th day of gestation to induce autistic phenotypes. The effect of ZNO at 30mg/Kg/p.o and 60mg/Kg/p.o on VPA-induced neurobehavioural anomalies (open field test, rotarod, forced swim test, and y-maze), oxidative stress (lipid peroxidation (LPO), total nitric oxide (NO)), altered antioxidative status (reduced glutathione (GSH), vitamin C (Vit-C) and catalase (CAT)), and histopathological staining (H&E staining) were assessed. Autistic behavioural anomalies were substantially diminished in a dose-dependent manner following ZNO administration. VPAexposed female pups had elevated levels of LPO and total NO, which were significantly attenuated by ZNO. Treatment with ZNO also substantially promoted the levels of GSH, Vit-C, and CAT in the cerebellum. In the present study, for the first time, we report that ZNO showed promising results in attenuating VPA-induced symptoms, indicating a possible neuroprotective effect against the core symptoms of autistic female F1 rat pups. Keywords Neuroprotection, Autism Spectrum Disorder, Zingerone, Oxidative Stress, Anti-oxidant, H&E staining