Phytochemical-Enriched Walnut Energy Bar Attenuates Chlorpromazine-Induced Neurotoxicity via Modulation of Oxidative Stress and TNF-α-Mediated Inflammation

Objective:This study aimed to investigate the neuroprotective activity of a walnut-based energy bar in drug-induced Parkinsonism in rats.Methodology:Wistar rats (n = 24) were divided into four groups: control (standard diet), disease (standard diet + chlorpromazine 3 mg/kg, intraperitoneal), standard treatment (standard diet +carbidopa+ levodopa (100 + 25 mg/kg, oral)), and walnut energy bar-treated (standard diet + walnut energy bar 1 g/kg/day for one month). Motor functions were assessed using standard behavioral tests. The antioxidant potential of the energy bar was analyzed using the 2, 2-Diphenyl-1-picrylhydrazyl (DPPH) assay. The walnut energy bar was analyzed by gas chromatography-mass spectrometry (GC-MS), confirming the presence of bioactive compounds, and high-performance liquid chromatography (HPLC) was used to quantify ferulic acid and cinnamic acid. Tumor necrosis factor-alpha (TNF-α), glutathione (GSH), catalase (CAT), superoxide dismutase (SOD), and malondialdehyde (MDA) levels were measured, and histopathological examination was performed on rat brain tissue.Results:Parkinsonism was successfully induced in rats, as evidenced by motor dysfunction, higher TNF-α and MDA levels, and lower GSH, along with a decline in antioxidant defense mechanisms (CAT, SOD). These biochemical alterations were improved in the walnut energy bar-treated group, suggesting neuroprotective and anti-inflammatory effects. Bioactive compounds identified by GC–MS, along with ferulic and cinnamic acids quantified by HPLC, were associated with the neuroprotective potential of the bar. Enzyme-linked immunosorbent assay (ELISA) and oxidative stress markers further supported these findings. These results were further validated by histopathological findings that showed neurodegeneration in the disease group and preserved neuronal architecture in the group treated with the walnut energy bar.Conclusion:The walnut energy bar-treated group exhibited significant neuroprotective, antioxidant, and anti-inflammatory activity. These findings suggest that a functional walnut energy bar may serve as a dietary intervention for managing drug-induced Parkinsonism symptoms.