Maslinic acid prevents IL‐1β‐induced inflammatory response in osteoarthritis via PI3K/AKT/NF‐κB pathways

Abstract

Osteoarthritis (OA) is a degenerative joint disease characterized by destruction of articular cartilage. The inflammatory response is the most important factor affecting the disease process. As interleukin-1β (IL-1β) stimulates several key mediators in the inflammatory response, it plays a major role in the pathogenesis of OA. Maslinic acid (MA) is a natural compound distributed in olive fruit. Previous studies have found that maslinic acid has an inhibitory effect on inflammation, but its specific role in the progression of OA disease has not been studied so far. In this study, we aim to assess the protective effect of MA on OA progression by in vitro and in vivo experiments. Our results indicate that, in IL-1β-induced inflammatory response, MA is effective in attenuating some major inflammatory mediators such as nitric oxide (NO) and prostaglandin E2, and inhibits the expression of IL-6, inducible nitric oxide synthase, cyclooxygenase-2, and tumor necrosis factor-α (TNF-α) in a concentration-dependent manner. Also, MA downregulated the expression levels of thrombospondin motif 5 (ADAMTS5) and matrix metalloproteinase 13 in chondrocytes, resulting in reduced degradation of its extracellular matrix. Mechanistically, MA exhibits an antiinflammatory effect by inactivating the PI3K/AKT/NF-κB pathway. In vivo, the protective effect of MA on OA development can be detected in a surgically induced mouse OA model. In summary, these findings suggest that MA can be used as a safe and effective potential OA therapeutic strategy.

Aldehyde dehydrogenase 2 alleviates monosodium iodoacetate-induced oxidative stress, inflammation and apoptosis in chondrocytes via inhibiting aquaporin 4 expression

“…During oxidative stress, high ROS levels trigger lipid peroxidation and the formation of an end-product of oxidation MDA, which influences the activities of antioxidant enzymes, such as SOD and ALDH [ 21 , 22 ]. Increasing evidence suggests that pro-inflammatory cytokines, such as IL-6, TNF-α and IL-1β, release from the inflammatory synovial tissue and synovial fluid to inhibit chondrocyte proliferation, which induces the apoptosis of chondrocyte and ultimately results in articular cartilage degeneration [ 23 , 24 ]. A clinical trial performed in patients of KOA demonstrated that curcuma longa extract administration brings significant clinical improvement the attenuation of oxidative stress and inflammation [ 25 ].…”

Angelicin Alleviates Post-Trauma Osteoarthritis Progression by Regulating Macrophage Polarization via STAT3 Signaling Pathway

“…To confirm the protective effect of angelicin, DMM models were established as previously described ( Chen et al, 2021 ). According to the previous studies protocol, the induced DMM model is similar to the pathological process of human joint damage.…”

“…After dehydration, embedding and cutting, the slides were stained with Safranin-O/Fast Green and hematoxylin and eosin (H&E). An experienced histological investigator blinded to evaluate medial femoral condyle and medial tibial plateau according to the International Osteoarthritis Research Society International (OASRI) scoring system as described previously ( Chen et al, 2021 ).…”

Role of Physical Exercise and Nutraceuticals in Modulating Molecular Pathways of Osteoarthritis

“…Olive oil polyphenols (OOPs), as oleocanthal (OC), oleuropein (OP), tyrosol (TY), and hydroxytyrosol (HT), could modulate inflammatory and degenerative OA molecular patterns. OOPs inhibit pro-inflammatory genes expression through the suppression of NF-κB and MAPK activation, while enhancing Nrf-2 signaling [ 125 , 126 , 127 , 128 ].…”