Luteolin and neuroinflammation: a multi-target therapeutic strategy for central nervous system disorders

Neuroinflammation is a fundamental pathological hallmark driving the initiation and progression of various neurological disorders. Luteolin, a natural flavonoid abundant in medicinal plants, fruits, and vegetables, exerts multifaceted neuroprotective effects across diverse experimental disease models. Its beneficial activities are mediated through complementary mechanisms, including suppression of aberrant microglial activation, modulation of pro-inflammatory signaling pathways, and enhancement of endogenous antioxidant defenses. These integrated actions attenuate inflammatory mediator release, reduce oxidative stress-induced neuronal damage, and inhibit apoptosis, thereby counteracting neuroinflammation-driven pathology. This review synthesizes current knowledge on luteolin's protective roles in central nervous system (CNS) disorders. It elucidates underlying molecular mechanisms, encompassing regulation of key signaling cascades such as NF-κB, MAPK, and Nrf2, as well as its impact on cellular processes including autophagy and mitochondrial function. Critical challenges hindering clinical translation-notably limited oral bioavailability and restricted blood-brain barrier (BBB) permeability-are systematically discussed to guide future research. A comprehensive understanding of luteolin's pleiotropic pharmacological actions will not only enhance knowledge of its therapeutic potential but may also facilitate the development of novel preventive and therapeutic strategies for neuroinflammatory and neurodegenerative diseases.