Behavioural and oxidative effects of Melissa officinalis leaf ethanol extract in a valproic acid-induced rat model of autism spectrum disorder

Abstract

Purpose: To determine the effect of ethanolic leaf extract of Melissa officinalis on the behavioral and oxidative stress parameters in a prenatal valproic acid (VPA) induced rat model of autism spectrum disorder. Methods: Pregnant Wistar rats were administered VPA (600 mg/kg, subcutaneously) or saline on gestational day 12.5. Control dams (saline group) received an equivalent volume of 0.9 % normal saline subcutaneously on the same gestational day. The male offspring were then administered 100 mg/kg of M. officinalis extract orally or vehicle (tap water) daily on postnatal days 35 - 82. Social behavior assessment was performed on postnatal day 1, and hippocampal biochemical analysis was conducted on the 10th day across four groups (n = 5 rats per group). Results: Gas chromatography-mass spectrometry (GC-MS) phytochemical analysis revealed the presence of eight major constituents, with α-terpineol being dominant (29.898 %). Prenatal exposure to VPA resulted in severe social deficit with a negative sociability index (-0.286 ± 0.225 vs. 0.36 ± 0.116 in controls) and social novelty index (-0.33 ± 0.295 vs. 0.841 ± 0.089 in controls). This social deficit was completely restored by M. officinalis treatment (p < 0.05). Valproic acid administration reduced superoxide dismutase activity by 41.3 % and malondialdehyde by 70.3 % compared to control, thereby resulting in severe oxidative stress in the hippocampus due to reduction of glutathione levels by 17.4 %. This process was also reversed by the administration of M. officinalis. Conclusion: Melissa officinalis extract reverses core autism-like social behavioral impairments and exhibits significant antioxidant and neuroprotective effects. This study justifies its ethnomedical therapeutic application.