Mechanistic Insights into the Neuroprotective Potential of Luteolin: An Overview.

Neurodegenerative disorders, such as Alzheimer's and Parkinson's diseases, are characterized by pathologies such as oxidative stress, neuroinflammation, mitochondrial dysfunction, and protein aggregation. Luteolin, a natural flavonoid, is known for its neuroprotective properties, targeting key pathological mechanisms. This review highlights the multi-target effects of luteolin, as demonstrated by in vitro and in vivo studies. Luteolin reduces oxidative damage by scavenging ROS, enhancing antioxidant enzymes, such as SOD, CAT, and GPx, and activating the Nrf2/ARE pathway. It reduces neuroinflammation by inhibiting NF-κB, AP-1, and JNK signalling and by lowering pro-inflammatory cytokines such as TNF-α and IL-1β. Luteolin maintains mitochondrial membrane potential, modulates apoptotic pathways via Bcl-2/Bax and PI3K/Akt signalling, and promotes autophagy by upregulating LC3-II and modulating the p62-Keap1-Nrf2 axis. It disrupts amyloidogenic and tau hyperphosphorylation pathways, inhibits AChE activity, enhances cholinergic transmission, and improves cognitive function by upregulating CREB, BDNF, and synaptic proteins. Although promising, these effects have been observed mainly in preclinical models, with limited clinical evidence. Future research should focus on the clinical validation and improvement of delivery systems to enhance brain bioavailability. This review provides a foundation for the development of luteolin as a therapeutic candidate for neurodegenerative diseases.