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

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.

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.

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.

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

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