Premium
Trihydroxyflavones with antioxidant and anti‐inflammatory efficacy
Author(s) -
Gomes Ana,
Couto Diana,
Alves Andreia,
Dias Irene,
Freitas Marisa,
Porto Graça,
Duarte José Alberto,
Fernandes Eduarda
Publication year - 2012
Publication title -
biofactors
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.204
H-Index - 94
eISSN - 1872-8081
pISSN - 0951-6433
DOI - 10.1002/biof.1033
Subject(s) - reactive oxygen species , chemistry , reactive nitrogen species , proinflammatory cytokine , antioxidant , anti inflammatory , arachidonate 5 lipoxygenase , cyclooxygenase , pharmacology , enzyme , biochemistry , inflammation , arachidonic acid , immunology , biology
Abstract The classical anti‐inflammatory therapies are frequently ineffective and present numerous and severe side effects, especially in long term use, which requires the development of anti‐inflammatory drugs with different scaffolds and mechanisms of action. Owing to the high antioxidant potential and anti‐inflammatory activities already inferred for hydroxyflavones, we found it would be relevant to evaluate the anti‐inflammatory potential of a series of trihydroxyflavones by testing their ability to scavenge reactive oxygen species (ROS) and reactive nitrogen species (RNS) in cells and cell‐free systems and to inhibit the proinflammatory pathways mediated by the enzymes cyclooxygenase (COX) and 5‐lipoxygenase (5‐LOX), in which reactive species have a proven involvement. The tested trihydroxyflavones proved to be effective inhibitors of neutrophils' oxidative burst and were shown to scavenge different ROS and RNS in cell‐free systems. The most active compound in the majority of the assays was 3,3′,4′‐trihydroxyflavone, which was somehow expected due to the presence of the ortho ‐dihydroxy in the B‐ring, an important structural feature in terms of free radical scavenging activity. Additionally, the studied compounds were able to inhibit the production of leukotriene B 4 by 5‐LOX in activated neutrophils. 3,5,7‐Trihydroxyflavone was able to inhibit both COX‐1 and COX‐2, which makes it a dual inhibitor of COX and 5‐LOX pathways and, therefore, a promising candidate for a new therapeutic option in the treatment of inflammatory processes.