Naringenin attenuates inflammation and apoptosis of osteoarthritic chondrocytes via the TLR4/TRAF6/NF-κB pathway

作者：Yan Wang, Zhengzhao Li, Bo Wang, Ke Li, Jiaxuan Zheng · 发表于：PeerJ · 年份：2023 · DOI：10.7717/peerj.16307 · 被引用次数：22 · 研究领域：Natural product bioactivities and synthesis、Osteoarthritis Treatment and Mechanisms、Medicinal plant effects and applications

plants. Increasing evidence indicates that it has several properties of biological significance, such as anti-infection, sterilization, anti-allergy, antioxidant free radical, and anti-tumor. However, its effect on osteoarthritis has not been elucidated properly. In this study, the treatment of primary chondrocytes with interleukin (IL)-1β was found to increase the secretions of IL-6, tumor necrosis factor (TNF)-α, and cyclooxygenase-2 (COX-2). Further, the mRNA expression of matrix metalloproteinase ((MMP)3, MMP9, and MMP13), the protein expression of Recombinant A Disintegrin And Metalloproteinase With Thrombospondin 5 (ADAMTS5), and cell apoptosis increased; the protein expression of Collagen II decreased. The injury of primary chondrocytes induced by IL-1β was reversed under the intervention of naringenin; this reversal was dose-dependent. The mechanistic study showed that naringenin inhibited the toll-like receptor 4 (TLR4)/TNF receptor-associated factor 6 (TRAF6)/NF-κB pathway in IL-1β-stimulated primary cells, and LPS, a TLR4 activator, reversed this inhibitory effect. In addition, a mouse model of osteoarthritis was established and treated with naringenin. The results revealed that naringenin alleviated the pathological symptoms of osteoarthritis in mice, reduced the expression of TLR4 and TRAF6, and the phosphorylation of NF-κB in knee cartilage tissue. It also inhibited the secretion of inflammatory factors, reduced extracellular matrix degradation, and decreased th...