Acrylamide (ACR) is an environmental pollutant with well-demonstrated neurotoxic and neurodegenerative effects in both humans and experimental animals. The present study aimed to investigate the neuroprotective effect of Portulaca oleracea seeds extract (PSE) against ACR-induced neurotoxicity in rats and its possible underlying mechanisms. PSE was subjected to phytochemical investigation using ultra-high-performance liquid chromatography (UPLC) coupled with quantitative time of flight mass spectrometry (qTOF-MS). Multivariate, clustering and correlation data analyses were performed to assess the overall effects of PSE on ACR-challenged rats. Rats were divided into six groups including negative control, ACR-intoxicated group (10 mg/kg/day), PSE treated groups (200 and 400 mg/kg/day), and ACR + PSE treated groups (200 and 400 mg/kg/day, respectively). All treatments were given intragastrically for 60 days. PSE markedly ameliorated brain damage as evidenced by the decreased lactate dehydrogenase (LDL), increased acetylcholinesterase (AchE) activities, as well as the increased brain-derived neurotrophic factor (BDNF) that were altered by the toxic dose of ACR. In addition, PSE markedly attenuated ACR-induced histopathological alterations in the cerebrum, cerebellum, hippocampus and sciatic nerve and downregulated the ACR-inclined GFAP expression. PSE restored the oxidative status in the brain as indicated by glutathione (GSH), lipid peroxidation and increased total antioxidant capacity (TAC). PSE upregulated the mRNA expression of protein kinase B (AKT), which resulted in an upsurge in its downstream cAMP response element-binding protein (CREB)/BDNF mRNA expression in the brain tissue of ACR-intoxicated rats. All exerted PSE beneficial effects were dose-dependent, with the ACR-challenged group received PSE 400 mg/kg dose showed a close clustering to the negative control in both unsupervised principal component analysis (PCA) and supervised orthogonal partial least square discriminant analysis (OPLS-Da) alongside with the hierarchical clustering analysis (HCA). The current investigation confirmed the neuroprotective capacity of PSE against ACR-induced brain injury, and our findings indicate that AKT/CREB pathways and BDNF synthesis may play an important role in the PSE-mediated protective effects against ACR-triggered neurotoxicity.
Keywords: Acrylamide; BDNF; CREB; Histopathology; Metabolic profiling; Oxidative stress; Portulaca oleracea seeds; UPLC-qTOF-MS.