Autism spectrum disorder is a
neurodevelopmental disorder marked by repetitive behaviour, challenges in verbal and non-verbal communication, poor socio-emotional health, and
cognitive impairment. An increased level of
signal transducer and activator of transcription 3 (STAT3) and a decreased level of
peroxisome proliferator-activated receptor (
PPAR) gamma have been linked to
autism pathogenesis.
Guggulsterone (GST) has a
neuroprotective effect on autistic conditions by modulating these signalling pathways. Consequently, the primary objective of this study was to examine potential neuroprotective properties of GST by modulating JAK/STAT and
PPAR-gamma levels in intracerebroventricular
propionic acid (ICV PPA) induced experimental model of
autism in adult rats. In this study, the first 11 days of ICV-PPA
injections in rats resulted in
autism-like behavioural, neurochemical, morphological, and histopathological changes. The above modifications were also observed in various biological samples, including brain homogenate, CSF, and blood plasma. GST was also observed to improve
autism-like behavioural impairments in autistic rats treated with PPA, including locomotion, neuromuscular coordination, depression-like behaviour, spatial memory, cognition, and
body weight. Prolonged GST treatment also restored neurochemical deficits in a dose-dependent manner. Chronic PPA administration increased STAT3 and decreased
PPAR gamma in autistic rat brain, CSF, and blood plasma samples, which were reversed by GST. GST also restored the gross and histopathological alterations in PPA-treated rat brains. Our results indicate the
neuroprotective effects of GST in preventing
autism-related behavioural and neurochemical alterations.