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.

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.

骨关节炎（OA）是一种慢性退行性关节疾病，受NF-κB信号通路触发的炎症反应极大地影响。Alpinetin（APT）是一种天然的类黄酮化合物，据报道具有许多重要的生物学活性，例如抗菌，抗肿瘤和抗炎。然而，其对OA中软骨细胞作用的作用尚未阐明。在这项研究中，我们研究了APT的抗炎作用。通过CCK8研究了APT对大鼠软骨细胞的细胞活力和细胞毒性的影响。Western blotting，qRT-PCR和免疫荧光染色被用于阐明APT介导软骨细胞抗炎作用的分子机制和信号传导途径。大鼠内侧半月板（DMM）失稳，诱发OA模型，体内。这些结果表明，APT可以减少TNF-α诱导的MMP-13和ADAMTS-5的增加以及COL2A1水平的减少。APT拮抗TNF-α诱导的BCL-2和CDK1下调。进一步的研究表明，APT同时抑制p65的细胞核易位和IκB的磷酸化并激活ERK的磷酸化。在体内，APT抑制软骨基质降解。总之，APT似乎可以很好地调节软骨细胞的抗炎作用，使其成为有前景的OA治疗化合物。

山姜对TNF-α诱导的NF-κB活化的抑制作用导致大鼠软骨细胞OA软骨破坏的体外。TNF-α刺激TNF-α受体，激活细胞质IκBα激酶（IKKS），然后IKK被磷酸化，随后被泛素-蛋白酶体系统降解。NF-κB转移到细胞核并结合各种NF-κB调节启动子区域中的NF-κB识别位点。这触发了促炎和促凋亡的基因表达。然而，Alpinetin可以不同方式抑制NF-κB信号传导途径：APT抑制IκBα磷酸化，进一步阻止IκBα的磷酸化泛素化。此外，APT阻止活化的NF-κB向细胞核的移位，以保护软骨组织免受损害。