关节软骨退化是骨关节炎（OA）的一种特征性病理变化。蒙脱石酸（PA）是杭子梢内所含的一种活性成分。先前的研究表明PA在多种疾病中具有抗炎效果。然而，PA在OA中的作用及其潜在机制尚未明确阐明。在本研究中，我们通过细胞实验和动物实验，调查了PA在OA上的潜在保护作用。PA抑制了干扰素-1β诱导的软骨细胞中的炎症介质生成，包括一氧化氮、诱导型一氧化氮合酶、前列腺素E2、环氧酶-2、肿瘤坏死因子α和白细胞介素-6。同时，PA还逆转了IL-1β处理的软骨细胞中基质金属蛋白酶-3和血小板聚集素结构域5的上调，以及胶原类型II和软骨素的下调。从机制上看，我们的发现表明，PA介导的SIRT6的过表达抑制了NF-κB信号通路。在体内，PA有助于改善小鼠OA模型中软骨损伤。总之，通过促进SIRT6表达和抑制NF-κB信号通路，PA抑制了IL-1β诱导的炎症和细胞外基质的退化，这表明PA对于OA的治疗是有益的。版权所有 © 2023 Elsevier B.V. 发布

Articular cartilage degeneration is a characteristic pathological change of osteoarthritis (OA). Pachymic acid (PA) is an active ingredient found in Poria cocos. Previous studies have shown that PA has anti-inflammatory effects on a variety of diseases. However, the role of PA in OA and its underlying mechanisms has not been clearly elucidated. In this study, we investigated potential protective effect of PA on OA through cell experiments in vitro and animal experiments in vivo. PA inhibited interleukin-1β-induced inflammatory mediator production in chondrocytes, which includes nitric oxide, inducible nitric oxide synthase, prostaglandin E2, cyclooxygenase-2, tumor necrosis factor alpha and interleukin-6. Meanwhile, PA also reversed the up-regulation of matrix metalloproteinase-3 and thrombospondin motifs 5, and the down-regulation of collagen type II and aggrecan in IL-1β-treated chondrocytes. Mechanistically, our findings revealed that PA-mediated overexpression of SIRT6 inhibited the NF-κB signaling pathway. In vivo, PA contributes to improve cartilage damage in the mouse OA model. In summary, PA inhibited IL-1β-induced inflammation and extracellular matrix degeneration by promoting SIRT6 expression and inhibiting the NF-κB signaling pathway, which indicates that PA is beneficial for the treatment of OA.Copyright © 2023. Published by Elsevier B.V.