LAUSR

Osteoarthritis (OA) is a chronic degenerative joint disease which is greatly affected by the inflammatory response triggered by the NF-κB signaling pathway. Alpinetin (APT) is a natural flavonoid compound, which has been reported to have many important biological activities such as antibacterial, antitumor, and anti-inflammatory. However, the action of its effect on chondrocytes in OA has yet to be elucidated. In this study, we investigated APT’s anti-inflammatory action. The effects of APT on cell viability and cytotoxicity of rat chondrocytes was investigated by CCK8. Western blotting, qRT-PCR, and immunofluorescent staining were used to elucidate the molecular mechanisms and signaling pathways of APT mediating anti-inflammatory effects on chondrocytes. An OA model was induced by destabilization of the medial meniscus (DMM) in rats, then APT was injected into the knee articular cavity to examine its anti-inflammatory effects in vivo. These results showed that APT could reduce the TNF-α-induced increase of MMP-13 and ADAMTS-5 and decrease of COL2A1 levels. APT antagonized TNF-α-induced down-regulation of BCL-2 and CDK1. Further studies have shown that APT simultaneously repressed cell nucleus translocation of p65 and the phosphorylation of IκB and activated the phosphorylation of ERK. In vivo, APT suppressed cartilage matrix degradation. In conclusion, APT appears to favorably modulate anti-inflammatory effects in chondrocytes making it a promising compound for OA treatment. Graphical Abstract Inhibitory effects of Alpinetin on TNF-α-induced NF-κB activation resulted in destruction of cartilage in rat OA chondrocytes in vitro. The TNF-α receptor were stimulated by TNF-α, activating the cytoplasmic IκBα kinases(IKKS), then IKKs will be phosphorylated, and subsequently degraded by the ubiquitin-proteasome system. NF-κB transfer to the nucleus and bind various NF-κB regulates the NF-κB recognition site in the promoter region. Which triggers the gene expression of pro-inflammatory and pro-apoptotic. However, Alpinetin could inhibits the NF-κB signaling pathway in different ways: APT inhibits IκBα phosphorylation, preventing phosphorylated ubiquitination of IκBα further. Moreover, APT blocks translocation of the activated NF-κB to the nucleus, to protect the cartilage tissue from damage. Inhibitory effects of Alpinetin on TNF-α-induced NF-κB activation resulted in destruction of cartilage in rat OA chondrocytes in vitro. The TNF-α receptor were stimulated by TNF-α, activating the cytoplasmic IκBα kinases(IKKS), then IKKs will be phosphorylated, and subsequently degraded by the ubiquitin-proteasome system. NF-κB transfer to the nucleus and bind various NF-κB regulates the NF-κB recognition site in the promoter region. Which triggers the gene expression of pro-inflammatory and pro-apoptotic. However, Alpinetin could inhibits the NF-κB signaling pathway in different ways: APT inhibits IκBα phosphorylation, preventing phosphorylated ubiquitination of IκBα further. Moreover, APT blocks translocation of the activated NF-κB to the nucleus, to protect the cartilage tissue from damage.