Naturally Occurring and Synthetic Coumarin Derivatives: Promising Agents for Managing Neuroinflammation.

Introduction/objective: Neuroinflammation is characterized by the activation of the brain's immune system, mainly involving microglia and astrocytes, in response to injury, infection, or neurodegenerative processes. It leads to neuronal damage, playing a key role in the onset and progression of neurological disorders. Lipopolysaccharide (LPS)-induced models have become pivotal in the study of neuroinflammation and its related complications. Coumarin derivatives-both natural and synthetic derivatives- have shown a promising effect on neuroinflammatory pathways.

Methods: This review studied findings from published studies on naturally occurring and synthetic coumarin derivatives with anti-neuroinflammatory activity. Literature was surveyed by Google Scholar, Scopus, PubMed, and Web of Science without date restrictions. Specific emphasis was placed on compounds evaluated using BV2 microglial cells and LPS-induced inflammation models.

Results: Coumarins demonstrated significant inhibitory effects on key inflammatory mediators, including nitric oxide (NO), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and cytokines like TNF-α and IL-6. Natural compounds such as kellerin and ferulaferone B, and synthetic agents like compounds 28 and 38, exhibited potent activity, often surpassing reference drugs. Compounds like 7-methoxycoumarin and 4-methylesculetin, both commercially available, have shown strong efficacy in animal studies.

Discussion: Coumarins exhibited multitarget mechanisms, making them promising candidates for managing neuroinflammation.

Conclusions: Translation of coumarins to clinical use requires further research to ensure safety and effectiveness.