Osteoarthritis (OA) remains a prevalent chronic disease without effective prevention and treatment. Amentadione (YP), a meroditerpenoid purified from the alga Cystoseira usneoides, has demonstrated anti-inflammatory activity. Here, we investigated the YP anti-osteoarthritic potential, by using a novel OA preclinical drug development pipeline designed to evaluate the anti-inflammatory and anti-mineralizing activities of potential OA-protective compounds. The workflow was based on in vitro primary cell cultures followed by human cartilage explants assays and a new OA co-culture model, combining cartilage explants with synoviocytes under interleukin-1β (IL-1β) or hydroxyapatite (HAP) stimulation. A combination of gene expression analysis and measurement of inflammatory mediators showed that the proposed model mimicked early disease stages, while YP counteracted inflammatory responses by downregulation of COX-2 and IL-6, improved cartilage homeostasis by downregulation of MMP3 and the chondrocytes hypertrophic differentiation factors Col10 and Runx2. Importantly, YP downregulated NF-κB gene expression and decreased phosphorylated IkBα/total IkBα ratio in chondrocytes. These results indicate the co-culture as a relevant pre-clinical OA model, and strongly suggest YP as a cartilage protective factor by inhibiting inflammatory, mineralizing, catabolic and differentiation processes during OA development, through inhibition of NF-κB signaling pathways, with high therapeutic potential.
Abstract:The present study was conducted to evaluate the antinociceptive and anti-inflammatory activities of methanol extract of rachis of Ormosia coccinea (Aubl.) Jacks (MEOC) using animal models of nociception and inflammation. The antinociceptive activity of the extract was assessed using acetic acid-induced abdominal writhing, hot-plate, and formalin tests. Oral administration of MEOC (500 mg/kg) produced significant (p < 0.05) antinociceptive effects when tested in mice using acetic acid-induced abdominal writhing test and on the inflammatory phase of the formalin test. It was also demonstrated that MEOC had no significant effect on the response latency time to the heat stimulus in the thermal model of the hot plate test. The anti-inflammatory activity of the extract was assessed using carrageenan, histamine and serotonin induced oedema in rat paw. The oral administration of MEOC showed maximum inhibition (64.29%) at 1 h on carrageenan edema, but it did not modify the edema induced by histamine and serotonin. The present results suggest that MEOC has a peripheral antinociceptive and anti-inflammatory action.
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