Coumarins derivatives and inflammation: Review of their effects on the inflammatory signaling pathways.

Natural and synthetic coumarins have been extensively described in the literature as effective drugs with several pharmacological activities. Many valuable publications have shown the anti-inflammatory potential of these compounds suggesting that coumarins could be an interesting scaffold for developing new therapeutic anti-inflammatory agents. However, despite the continuous efforts of research in this field, no major breakthrough was yet achieved and only a few coumarin-like drugs are commercially available. In the present article, we reviewed the most relevant studies conducted in the last two decades (2000-2021) and presenting evidence for the anti-inflammatory mechanisms of coumarins. The review provides a comprehensive survey of scientific research revealing through multiple in vitro and in vivo models the effect of natural and synthetic coumarins on components of the Toll-like receptors (TLR), Janus Kinase/Signal Transducer and Activator of Transcription (JAK/STAT), Inflammasomes, mitogen-activated protein kinase (MAPK), nuclear factor- κ-light-chain-enhancer of activated B cells (NF- κB) and transforming growth factor-β/small mothers against decapentaplegic (TGF-β/SMAD) pathways.