Oleacein Attenuates Lipopolysaccharide-Induced Inflammation in THP-1-Derived Macrophages by the Inhibition of TLR4/MyD88/NF-κB Pathway

It is known that plant phenolic compounds exert anti-inflammatory activity through both
anti-oxidant effects and modulation of pivotal pro-inflammatory factors. Recently, Olea europaea
has been studied as a natural source of bioactive molecules; however, few studies have focused
on the biological effect of oleacein (OLC), the most abundant secoiridoid. Therefore, the aim of
this study was to investigate the potential anti-oxidant activity of OLC, as well as to study its
anti-inflammatory effect in lipopolysaccharide (LPS)-stimulated THP-1-derived macrophages. LPS
brought a dramatic increase of both release and gene expression of pro-inflammatory cytokines (IL-6,
IL-1β and TNF-α), as well as a decrease of anti-inflammatory ones (IL-10), the effects of which are
reverted by OLC. Moreover, it reduced the levels of COX-2, NO and PGE2 elicited by LPS exposure
in THP-1 macrophages. Interestingly, OLC modulated inflammatory signaling pathways through
the inhibition of CD14/TLR4/CD14/MyD88 axis and the activation of NF-κB. Finally, OLC showed
relevant anti-oxidant capability, assessed by abiotic assays, and reduced the intracellular amount
of ROS generated by LPS exposure in THP-1 macrophages. Overall, these results suggest that the
anti-oxidant activity and anti-inflammatory effect of OLC may cooperate in its protective effect
against inflammatory stressors, thus being a possible alternative pharmacological strategy aimed at
reducing the inflammatory process.