Luteolin attenuates cadmium neurotoxicity by suppressing glial inflammation and supporting neuronal survival

Cadmium (Cd), a neurotoxic metal, is associated with the development of neurological disorders. This study investigated the neuroprotective effects of Luteolin against Cd-induced toxicity in cultured cells and mouse models. Our findings demonstrate that Luteolin protects hippocampal neurons from Cd toxicity and mitigates Cd-triggered inflammatory responses in microglial BV2 cells. In Cd-exposed mice, symptoms such as weight loss, motor retardation, multi-organ damage, and cognitive deficits were observed. Remarkably, Luteolin treatment reversed these effects, repaired organ damage, and restored learning and memory abilities. Mechanistically, Cd toxicity induced significant upregulation of pro-inflammatory factors and neuroinflammation in the hippocampus and prefrontal cortex, including elevated glial cell markers (IBA1, GFAP, and CD68) and reduced neuronal marker MAP2. Luteolin counteracted these adverse effects by inhibiting the Notch1/Hes1 inflammatory signaling axis and restoring the BDNF-TrkB/AKT1 signaling axis, thereby promoting neuronal survival. These results highlight the potential of Luteolin as a natural neuroprotective agent against Cd-induced neurotoxicity, offering a promising therapeutic strategy for mitigating Cd-related neurological damage.