In Vitro and In Vivo Experimental Model-based Approaches for Investigating Anti-inflammatory Properties of Coumarins

Coumarins are polyphenolic compounds that are often used to treat inflammatory conditions in complementary and alternative medicine.In this study, we reviewed reports of in vivo and in vitro experimental modelbased approaches investigating the potential anti-inflammatory properties of coumarins.A literature search of PUBMED, MEDLINE, Web of Science, and Scopus was performed covering the period from 1 January 2005 to 31 December 2015. The keywords used to search were 'anti-inflammatory' and 'coumarin' and 'in vivo' or 'in vitro'. This search identified 425 article titles.Of the 425 article titles, 127 full-text articles were reviewed, and 69 of them were included in the analysis. Most of the studies (81.2%) used in vitro assays. The studies focused on cytokines such as tumour necrosis factor (TNF), interleukin (IL)-6, and IL-1-β (55.1%), as well as oedema (46.5%), nitric oxide (NO, 23.2%), oxidative stress (21.7%), inflammatory cells (21.7%), nuclear factor (NF)-κB (24.6%), mitogen-activated protein kinase (MAPK, 13%), myeloperoxidase (MPO, (15.9%), cyclooxygenase (COX)-2 (14.5%), prostaglandin E2 (PGE2, 8.7%), 5-lipoxygenase (LOX, 4.3%), and adhesion molecules (7.2%). Coumarins inhibited all these parameters except for IL-10, nuclear factor erythroid 2 (NFE2)-related-factor 2 (Nrf2), and regulatory T cell (Treg) differentiation.In vitro methods were the most commonly used to study the antiinflammatory effects of coumarins. The results showed that coumarins exerted antiinflammatory and antioxidant activities by inhibiting NF-κB, nuclear factor of activated T cells (NFAT), retinoic acid-related orphan receptor γτ (RORγτ), and MAPK and increasing Nrf2 activation. These results suggest that coumarins could be important candidates for the development of novel anti-inflammatory therapeutic drugs.