Coreopsis tinctoria Nutt. polyphenols attenuate acrylamide-induced cerebral injury via dual modulation of Nrf2/HO-1 and MAPK pathways

BACKGROUND Acrylamide (ACR), an environmental neurotoxicant prevalent in thermally processed foods, contributes to brain injury via oxidative stress and neuroinflammation. The cumulative effects of long-term low-dose exposure are particularly alarming. As a traditional food ingredient, the inflorescence of Coreopsis tinctoria Nutt. is rich in polyphenolic compounds that exhibit significant anti-inflammatory and antioxidant properties. This study systematically evaluated the neuroprotective potential of Coreopsis tinctoria Nutt. polyphenols (CTNP) against chronic low-dose ACR exposure in mice. RESULTS Behavioral analyses demonstrated that CTNP (0.25–1.00 g kg −1 ) significantly ameliorated ACR-induced gait abnormalities and restored voluntary activity. CTNP mitigated neuronal misalignment and loss of synaptic density in the hippocampal CA1/CA3 regions and markedly reduced serum levels of brain injury markers MBP and GFAP by 30.6% and 41.7%, respectively. Mechanistic investigations revealed that CTNP attenuated oxidative damage via activation of the Nrf2/HO-1 pathway, leading to decreased brain reactive oxygen species and malondialdehyde levels while enhancing catalase, superoxide dismutase and glutathione peroxidase activities. Furthermore, CTNP suppressed MAPK pathway-mediated neuroinflammation, reducing pro-inflammatory factors such as COX-2, TNF- α and IL-1 β . CONCLUSION These findings demonstrate that CTNP, as diet-derived bioactives, mitigate ACR neurotoxicity through coordinated modulation of Nrf2/HO-1 antioxidant and MAPK anti-inflammatory pathways, supporting their potential as a functional food component for preventing environmental toxicant-associated neural damage. © 2026 Society of Chemical Industry.