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



Ghafouri SN ; Dastyafteh N ; Iraji A ; Mahdavi M ; Saeedi M
Source: Mini-Reviews in Medicinal Chemistry Published:2026

Abstract

Introduction 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 for studying neuroinflammation and its related complications. Coumarin derivatives, both natural and synthetic, have shown promising effects 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 in English-language papers from Google Scholar, Scopus, PubMed, and Web of Science, without date restrictions, using the following search strategies: “coumarins” and “neuroinflammation” and “BV2-cell” or “Microglia” or “Neurodegenerative disorder”. 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 (1) and ferusingensine G (2), compound 17, and synthetic agents such as compounds 31 and 41, exhibited potent activity, often higher than that of 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. Conclusion Translation of coumarins to clinical use requires further research to ensure safety and effectiveness. 2026, Bentham Science Publishers