Oleocanthal Inhibits Catabolic and Inflammatory Mediators in LPS-Activated Human Primary Osteoarthritis (OA) Chondrocytes Through MAPKs/NF-κB Pathways

Abstract

Background/Aims: Oleocanthal (OC), a phenolic compound present in extra virgin olive oil (EVOO), has attracted attention since its discovery for its relevant pharmacological properties in different pathogenic processes, including inflammation. Here, we investigated the involvement of OC in LPS-activated osteoarthritis (OA) human primary chondrocytes. Methods: Human primary chondrocytes were harvested from articular cartilage samples obtained from OA patients. The effects of OC on the viability of chondrocytes were tested by MTT assay. Protein and mRNA expression of several catabolic and pro-inflammatory factors after OC treatment were measured by RT-qPCR and western blot respectively. Moreover, we analysed the NO production by Griess reaction. Finally, several pathways mediators were analysed by western blot. Results: We demonstrated that OC did not have any cytotoxic effect. Oleocanthal inhibited NO production and strongly decreased NOS2 and COX-2 protein and mRNA expression in LPS-activated human primary OA chondrocytes. Interestingly, OC also inhibits MMP-13 and ADAMTS-5. In addition, OC downregulates several pro-inflammatory factors, such as IL-6, IL-8, CCL3, LCN2 and TNF-α induced by LPS in human primary OA chondrocytes. Finally, we demonstrated that OC exerts its effects through the MAPK/P38/NF-kB pathways. Conclusion: These data show that OC is able to block LPS-mediated inflammatory response and MMP-13 and ADAMTS-5 induction in human primary OA chondrocytes via MAPKs/NF-kB pathways, suggesting that OC may be a promising agent for the treatment of inflammation in cartilage and a potential molecule to prevent disease progression by inhibiting metalloproteases and aggrecanases.

The Extra-Virgin Olive Oil Polyphenols Oleocanthal and Oleacein Counteract Inflammation-Related Gene and miRNA Expression in Adipocytes by Attenuating NF-κB Activation

“…In accordance with the early demonstration of an anti-inflammatory action of OC and OA by inhibiting the activity of the pro-inflammatory COX [33] and 5-lipoxygenase (LOX) [83] enzymes in cell-free enzymatic assays, as well as the expression of COX-2 in LPS-challenged human monocytes (with a 96% and 88% inhibition for OC and OA, respectively) [84] and chondrocytes [79], we here show that OC and OA were able to abolish COX-2 mRNA upregulation induced by TNF-α in human SGBS adipocytes. This effect could have therapeutic implications for obesity-related inflammation because COX-2-derived prostanoids, mainly prostaglandin E 2 (PGE 2 ), play a significant role in mediating macrophage infiltration and inflammation in the visceral fat and the development of AT and systemic insulin resistance and fatty liver [85,86].…”

“…A similar anti-inflammatory effect on gene expression of cytokines, chemokines and other pro-inflammatory markers has been previously found for both compounds in different cell models. OC was able to inhibit gene expression of IL-6, MIP-1α in murine chondrocytes and macrophages challenged with lipopolysaccharide (LPS), and IL-1β, IL-6, TNF-α, GM-CSF, IL-8, CCL3, LCN2, MMP-13, ADAMTS-5 in LPS-stimulated macrophages [78,79]. OA has been shown to inhibit TNF-α-and lipopolysaccharide (LPS)-induced MCP-1 and adhesion molecules (ICAM-1, VCAM-1, and E-selectin) mRNA expression in endothelial cells and consequent monocyte adhesion to the endothelium [36].…”

Icariin alleviates osteoarthritis by inhibiting NLRP3-mediated pyroptosis

“…OA is a progressive and deteriorative disorder of articular joint, and current medicines including acetaminophen, nonsteroidal anti-inflammatory drugs, and duloxetine were only able to relieve the pain and unable to cure the disease. Inflammation and apoptosis are associated with the progress of OA, and anti-inflammatory agents could prevent OA development [18][19][20][21]. ICA, the extract of Epimedium, is known to have anti-oxidative, anti-neuroinflammatory, and anti-apoptotic effects and considered to be effective for a range of disorders, such as neoplasm, Alzheimer's disease, cerebral ischemia, depression, diabetes, and Parkinson's disease (PD) [22][23][24][25].…”

Potential Protective Role Exerted by Secoiridoids from Olea europaea L. in Cancer, Cardiovascular, Neurodegenerative, Aging-Related, and Immunoinflammatory Diseases

“…It is well-known that thrombotic and cardiovascular disorders are linked to an imbalance in prostanoid homeostasis, particularly prostaglandin or thromboxane production, which are involved in vasodilatation or vasoconstriction, respectively, and platelet aggregation [162]. OLE has exerted strong inhibitory effects on COX-1 and COX-2 in several studies [50,163,164]; nevertheless, future studies are needed to confirm the property of OLE in cardiovascular disorders ( Table 3).…”