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

Abstract

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.

The Anticancer Effect of a Flavonoid-Rich Extract of Bergamot Juice in THP-1 Cells Engages the SIRT2/AKT/p53 Pathway

“…Afterwards, RNA extraction from untreated and treated cells was performed employing TRIzol reagent (Invitrogen, Carlsbad, CA, USA), according to the manufacturer’s protocol. An equal amount of total RNA (2 µg) for each sample was reverse transcribed into cDNA employing the High-Capacity cDNA Archive Kit (Applied Biosystems, Life Technologies, Foster City, CA, USA), as previously described [ 29 ]. Then, quantitative PCR reaction (qPCR) was carried out in a 96 well-plate, using a 7500 qPCR System (Applied Biosystems), in a total volume of 20 µL, including 1x SYBR ® Select Master Mix (Applied Biosystems), 0.2 µM of specific primers and 25 ng of RNA converted into cDNA.…”

Extra Virgin Olive Oil Secoiridoids Modulate the Metabolic Activity of Dacarbazine Pre-Treated and Treatment-Naive Melanoma Cells

“…Among the determined compounds, OCAL and OCEIN are particularly interesting considering their bioactive properties. OCAL is mainly recognized as a compound with neuroprotective activity in Alzheimer’s disease [ 58 ], although it also has anti-inflammatory and anticancer activities [ 59 , 60 , 61 ], while OCEIN is widely known for its antioxidative, anti-inflammatory, anti-atherosclerotic, and neuroprotective activities [ 62 , 63 , 64 ]. The concentration of OCAL in the analysed EVOOs ranged from 125 to 215 mg/kg EVOO, and the concentration of OCEIN was in the range of 125–330 mg/kg EVOO.…”

Dietary oleacein, a secoiridoid from extra virgin olive oil, prevents collagen-induced arthritis in mice

“…Additionally, our data are in agreement with Carpi et al, who demonstrated that OLA counteract obesity-associated adipocyte inflammation attenuating NF-κB activation in differentiated Simpson-Golabi-Behmel syndrome (SGBS) adipocytes 52 and in lipopolysaccharide-Induced Inflammation in THP-1-derived macrophages. 53 Similarly, MAPKs a family of serine/threonine protein kinases, have attracted considerable attention as potent therapeutic targets in RA. All three kinases families, JNK, p38 and extracellular signal-regulated kinase (ERK), are expressed in rheumatoid synovial tissue.…”