Combined Puerarin and Magnesium Acetyl Taurate Intervention Mitigates Autism-Like Pathology Through Glutamatergic and MAPK Pathway Regulation.

Autism is a multifactorial neurodevelopmental disorder characterized by social deficits, stereotypical behaviour, and neurotransmitter imbalance. This study evaluated the neuroprotective potential of Puerarin (PUN) and Magnesium Acetyl Taurate (MGAT) in a propionic acid (PPNA)-induced rat model of autism. PPNA was administered intracerebroventricularly for 11 consecutive days to induce autism-like features, followed by a 44-day treatment period with PUN (300 mg/kg, i.p.) and MGAT (500 mg/kg, p.o.). A comprehensive assessment was conducted, including behavioural analysis, biochemical and molecular evaluations, cerebrospinal fluid and plasma profiling, and histopathology. Treatment with PUN and MGAT, particularly in combination, improved behavioural outcomes, restored neurotransmitter balance, reduced neuroinflammation and apoptotic signaling, and attenuated activation of the glutaminase-glutamate/NMDAR and MAPK pathways (C-JNK, ERK1/2, P38 MAPK). Additionally, treatment increased magnesium levels and PSD-95 expression, indicating significant neuroprotection. These findings support the potential of PUN and MGAT as a multitarget therapeutic strategy for autism and warrant further translational investigation.