Administration with carnosic acid alleviates the development of osteoarthritis by attenuating macrophage polarization-mediated inflammation and cartilage oxidative damage and degradation via regulating Nrf2/NF-kB axis.
骨关节炎（OA）是一种常见的炎症性退行性关节疾病，以关节软骨退变为特征。巨噬细胞在OA的软骨损伤和滑膜炎症中发挥重要作用。鼠尾草酸（CA）在多种炎症性疾病中具有关键作用。用鼠尾草酸处理巨噬细胞。将软骨细胞与来自巨噬细胞的条件培养基（CM）共孵育。随后分析其对巨噬细胞极化的影响。探讨其对软骨细胞氧化损伤、炎症及细胞外基质（ECM）代谢失衡的影响。将鼠尾草酸给予前交叉韧带横断（ACLT）构建的OA小鼠模型。随后进一步探讨鼠尾草酸在OA进展中的疗效。鼠尾草酸抑制LPS诱导的巨噬细胞M1极化，并增强IL-4诱发的巨噬细胞M2样极化。此外，来自M1巨噬细胞的条件培养基（CM）诱导软骨细胞氧化损伤，而鼠尾草酸可消除这一效应。同时，鼠尾草酸抑制了M1巨噬细胞CM所致的炎症介质及炎症细胞因子IL-6和TNF-α含量增加。此外，鼠尾草酸还可拮抗M1巨噬细胞CM诱发的细胞外基质（ECM）降解。在机制上，鼠尾草酸增强Nrf2表达并抑制随后NF-κB信号通路的激活。有趣的是，抑制Nrf2可抑制NF-κB信号通路的激活，并逆转鼠尾草酸对巨噬细胞M1样极化的抑制作用。此外，鼠尾草酸减轻了M1巨噬细胞诱导的软骨细胞氧化损伤、炎症反应及ECM代谢紊乱。鼠尾草酸减轻了关节软骨退变和滑膜炎，导致骨关节炎研究学会国际（OARSI）评分和滑膜炎评分降低。此外，鼠尾草酸减轻了OA小鼠的氧化应激损伤和软骨降解。另外，鼠尾草酸影响OA小鼠滑膜巨噬细胞从M1向M2极化，减轻炎症及Nrf2/NF-κB轴的激活。鼠尾草酸可能通过调控Nrf2/NF-κB轴，减轻巨噬细胞极化介导的炎症反应和软骨氧化损伤，从而缓解OA的进展，支持其作为临床实践中OA患者一种有前景的潜在治疗药物。
Osteoarthritis (OA) is a common inflammatory degenerative joint disease characterized by deterioration of articular cartilage. Macrophages exert the important roles in cartilage damage and synovial inflammation in OA. Carnosic acid (CA) possesses critical function in multiple inflammatory diseases. Macrophages were treated with carnosic acid. Chondrocytes were incubated with conditioned medium (CM) from macrophages. Then, the effects on macrophage polarization were analyzed. The effects on chondrocyte oxidative injury, inflammation and extracellular matrix (ECM) metabolism imbalance were explored. Carnosic acid was administrated to Anterior cruciate ligament transection (ACLT)-constructed OA mice model. Then, the efficacy of carnosic acid in the progression of OA was further explored. Carnosic acid inhibited LPS-induced macrophage M1 polarization and enhanced IL-4-evoked macrophage M2-like polarization. Furthermore, conditioned medium (CM) from M1 macrophages induced chondrocyte oxidative injury, which were abrogated by carnosic acid. Concomitantly, carnosic acid restrained M1 macrophage CM-increased inflammatory mediator and inflammatory cytokine IL-6 and TNF-α contents. Moreover, carnosic acid also antagonized M1 macrophage CM-evoked extracellular matrix (ECM) degradation. Mechanistically, carnosic acid enhanced Nrf2 expression and suppressed subsequent activation of the NF-κB signaling. Intriguingly, Nrf2 inhibition restrained activation of the NF-κB signaling and reversed carnosic acid-mediated suppression on macrophage M1-like polarization. Furthermore, carnosic acid attenuated M1 macrophage-induced oxidative injury, inflammatory response and ECM metabolism disturbance of chondrocytes. , carnosic acid alleviated articular cartilage degeneration and synovitis, leading to decrease of Osteoarthritis Research Society International (OARSI) and synovitis scores. Moreover, carnosic acid attenuated oxidative stress injury and cartilage degradation in OA mice. Additionally, carnosic acid affected synovium macrophage polarization from M1 to M2 , mitigated inflammation and activation of the Nrf2/NF-kB axis in OA mice. Carnosic acid may alleviate the progression of OA by attenuating macrophage polarization-mediated inflammatory response and cartilage oxidative damage via regulating Nrf2/NF-kB axis, supporting it as a promising and potential therapeutic agent for patients with OA in clinical practice.
Yang Yang, Wenwen Ping, Jin Xu, Rong Yang. Administration with carnosic acid alleviates the development of osteoarthritis by attenuating macrophage polarization-mediated inflammation and cartilage oxidative damage and degradation via regulating Nrf2/NF-kB axis.. Frontiers in immunology. 2026; doi:10.3389/fimmu.2026.1710302.
Yang Yang, Wenwen Ping, Jin Xu, Rong Yang (2026). Administration with carnosic acid alleviates the development of osteoarthritis by attenuating macrophage polarization-mediated inflammation and cartilage oxidative damage and degradation via regulating Nrf2/NF-kB axis.. Frontiers in immunology. https://doi.org/10.3389/fimmu.2026.1710302
Yang Yang, Wenwen Ping, Jin Xu, Rong Yang. Administration with carnosic acid alleviates the development of osteoarthritis by attenuating macrophage polarization-mediated inflammation and cartilage oxidative damage and degradation via regulating Nrf2/NF-kB axis.[J]. Frontiers in immunology, 2026 doi:10.3389/fimmu.2026.1710302.
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