Betulinic acid (BA), a natural compound isolated from many medicinal plants known for neuroprotective properties, was assessed for its potential to mitigate autism-like symptoms in rat pups following prenatal exposure to sodium valproate. In this study, pregnant Wistar albino rats received a subcutaneous injection of sodium valproate at a dose of 400 mg/kg on gestation day 13 to model autism-like behaviours in their offspring. Behavioural parameters such as locomotion, stereotypy, affective responses (depression and anxiety), learning & memory, as well as social interaction were evaluated in rat pups from (PND) 1 to 20. Tests included a photo actometer, the marble-burying assay, the tail-suspension test, the elevated zero maze, the Morris water maze, and social interaction paradigms. From PND21 to PND35, oral administrations of BA were given at two doses (25 and 50 mg/kg), while reference treatments included Diazepam (4 mg/kg, i.p), Fluoxetine (10 mg/kg, i.p), and Donepezil (0.75mg/kg, i.p). On PND 36, brains were harvested for subsequent biochemical and antioxidant assessments. BA treatment significantly improved locomotor activity and decreased repetitive behaviour, elicited antidepressant and anxiolytic responses, along with improved cognitive and social functions relative to the sodium valproate group. Both doses of betulinic acid significantly attenuated oxidative stress, reduced glutamate levels, and suppressed acetylcholinesterase activity in brain tissue. The neuroprotective efficacy of BA in autistic rat pups was comparable to the reference drugs employed for various models. The phytoconstituent betulinic acid was associated with normalization of glutamate levels, inhibition of brain acetylcholinesterase activity, and antioxidant effects, which may contribute to the attenuation of autism-like phenotypes in valproate-exposed rat pups.
Pasrija et al. (Fri,) studied this question.