Plant-Derived Bioactive Compounds in Neuroinflammation: Molecular Mechanisms, Preclinical Evidence, and Translational Challenges

Neuroinflammation involves coordinated interactions among microglia, astrocytes, neurons, vascular cells, and peripheral immune signals and is implicated in diverse neurological disorders. This narrative review critically examines mechanistic, preclinical, and clinical evidence concerning plant-derived bioactive compounds from three recurrent chemical groups—phenolic compounds, terpenes and terpenoids, and alkaloids—identified through the review process. An iterative search of PubMed, ScienceDirect, Web of Science, and Scopus was combined with explicit eligibility, screening, and qualitative synthesis criteria. The reviewed evidence links specific compounds and characterized preparations with modulation of nuclear factor kappa B, mitogen-activated protein kinases, Janus kinase/signal transducer and activator of transcription signaling, and the NLR family pyrin domain containing 3 inflammasome, as well as nuclear factor erythroid 2-related factor 2/heme oxygenase 1, cannabinoid receptor 2, peroxisome proliferator-activated receptor gamma, neurotrophic factor-associated signaling, and phosphoinositide 3-kinase/protein kinase B-associated responses. Reported effects include changes in glial reactivity, inflammatory mediators, redox homeostasis, neuronal injury, and selected functional outcomes; however, they depend on compound identity, dose, formulation, cell type, stimulus, and experimental model. The evidence remains predominantly mechanistic and preclinical, whereas available clinical studies are limited and heterogeneous. Uncertain blood–brain barrier penetration and central nervous system exposure, formulation-dependent bioavailability, limited target-engagement data, safety considerations, and potential drug–drug interactions continue to constrain translation. Future studies should prioritize chemically defined interventions, disease-relevant human models, direct pharmacokinetic and target-engagement measurements, and clinical outcomes linked to neuroinflammation.