Background: Coumarins are polyphenolic compounds that are often used to
treat inflammatory conditions in complementary and alternative medicine.
Objective: In this study, we reviewed reports of in vivo and in vitro experimental modelbased
approaches investigating the potential anti-inflammatory properties of coumarins.
Methods: 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.
Results: 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.
Conclusion: 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.