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Osteoarthritis is a highly prevalent joint disease; however, effective treatments are lacking. Protopine (PTP) is an isoquinoline alkaloid with potent anti-inflammatory and antioxidant properties; however, it has not been studied in osteoarthritis. This study aimed to investigate whether PTP can effectively protect chondrocytes from ferroptosis. Primary mouse chondrocytes were treated with tert -butyl hydroperoxide (TBHP) to simulate oxidative stress in an in vitro model of osteoarthritis. Two concentrations of PTP (10 and 20 μg/mL) were validated for in vitro experiments. Cellular inflammation and metabolism were detected using RT-qPCR and western blotting (WB). Ferroptosis was assessed via WB, qPCR, reactive oxygen species (ROS) levels, lipid ROS, and immunofluorescence staining. In vitro, PTP significantly ameliorated chondrocyte inflammation and cytolytic metabolism and significantly suppressed chondrocyte ferroptosis through the activation of the Nrf2 pathway. The anterior cruciate ligament transection (ACLT) mouse model was used to validate the in vivo effects of PTP. The joint cartilage was assessed using the Osteoarthritis Research Society International (OARSI) score, Safranin O staining, and immunohistochemistry. The intra-articular administration of PTP alleviated cartilage inflammation and ferroptosis, as evidenced by the expression of MMP3, MMP13, COL2A1, GPX4, and Nrf2. Overall, we find that PTP exerted anti-ferroptosis and anti-inflammatory effects on chondrocytes to protect the articular cartilage. • PTP is an isoquinoline alkaloid with anti-inflammatory and antioxidant properties. • PTP significantly ameliorated chondrocyte inflammation and ferroptosis. • Repression of chondrocyte ferroptosis was mediated by activating the Nrf2 pathway. • PTP exerts these effects on chondrocytes to protect the articular cartilage. [ABSTRACT FROM AUTHOR]

Background: Osteoarthritis (OA) is widely recognized as the most common chronic joint disease accompanied by progressive cartilage and subchondral bone damage. Toddalolactone (TOD), a natural compound extracted from Toddalia asiatica (L.) Lam., has been widely used in the treatment of stroke, rheumatoid arthritis, and oedema. Nevertheless, what TOD acts as in the pathogenesis and progression of OA hasn't been reported. In this investigation, we have aimed to determine how TOD affects OA in vitro and in vivo. Methods: LPS (10 µg/ml) and IL-1β (10 ng/ml) were employed to induce chondrocyte inflammation or RANKL to induce osteoclast differentiation in bone marrow derived macrophages (BMMs). The effects of TOD on chondrocyte inflammation and osteoclast differentiation were evaluated. Anterior cruciate ligament transection (ACLT) was performed to develop an OA animal model and study the effects of TOD. Results: We found that TOD inhibited the expression of inflammatory and catabolic mediators (IL-6, IL-8, TNF-α, MMP2, MMP9, and MMP13) in inflammatory chondrocytes in vitro. Furthermore, TOD was proven to inhibit RANKL-induced-osteoclastogenesis and inhibit the expression of osteoclast marker genes. Our data also confirmed that TOD suppressed the destruction of articular cartilage and osteoclastogenesis via inhibiting the activation of NF-κB and MAPK signalling pathways. In the ACLT mouse model, we found that TOD attenuated cartilage erosion and inhibited bone resorption. Conclusions: These results showed that TOD can be adopted as a potential therapeutic agent for OA. [ABSTRACT FROM AUTHOR]

• EsA attenuates inflammation and catabolism of chondrocytes. • EsA restrains RANKL-induced osteoclast formation. • Treatment with EsA suppresses NF-κB and MAPK signalling pathway activation in vitro. • EsA protects OA cartilage in vivo and may be a novel therapeutic target. Osteoarthritis is a relatively common disorder of articular deterioration related to cartilage damage, subchondral bone remodelling, inflammation and metabolism. Agents that can inhibit cartilage degradation and osteoclastogenesis are required for the prevention and treatment of osteoarthritis. Esculentoside A, the highest concentration triterpene saponin isolated from the root of Phytolacca esculenta, has commonly been used for the treatment of chronic bronchitis. However, the role esculentoside A plays in ameliorating osteoarthritis has not been reported. We found that esculentoside A suppresses the expression of IL-1β-induced inflammatory and metabolic factors (IL-6, IL-8, TNF-α, MMP2, MMP3 and MMP13). In addition, esculentoside A restrains osteoclast formation by inhibiting the marker gene expression of NFATc1 and c-Fos. Our results indicate that esculentoside A markedly suppresses IL-1β-induced NF-κB and MAPK signalling pathway activation in chondrocytes, and inhibits RANKL-induced osteoclast precursor generation. Finally, treatment with esculentoside A inhibits the progressive cartilage degeneration and osteoclastogenesis in osteoarthritis mouse models. In summary, these results demonstrate that esculentoside A could be a latent therapeutic reagent for the treatment of osteoarthritis. [ABSTRACT FROM AUTHOR]