Department of Hand Surgery, Hainan General Hospital (Hainan Affiliated Hospital of Hainan Medical University), Haikou, China.
Department of Emergency Surgery, Hainan General Hospital (Hainan Affiliated Hospital of Hainan Medical University), Haikou, China.
PeerJ. 2023 Nov 8;11:e16307. doi: 10.7717/peerj.16307. eCollection 2023.
Naringenin is a flavonoid extracted from the seed coat of 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 the protein expression of cleaved caspase3. In conclusion, the findings of this study suggest that naringenin may be a potential option for the treatment of osteoarthritis.
柚皮素是一种从植物种子外壳中提取的类黄酮。越来越多的证据表明，它具有几种具有生物学意义的特性，如抗感染、杀菌、抗过敏、抗氧化自由基和抗肿瘤。然而，其对骨关节炎的作用尚未得到充分阐明。在这项研究中，发现白细胞介素（IL）-1β处理原代软骨细胞会增加白细胞介素-6（IL-6）、肿瘤坏死因子（TNF）-α和环氧化酶-2（COX-2）的分泌。此外，基质金属蛋白酶（MMP）3、MMP9 和 MMP13 的 mRNA 表达、重组 A 解整合素和金属蛋白酶与血小板反应蛋白 5（ADAMTS5）的蛋白表达以及细胞凋亡增加，而 Collagen II 的蛋白表达减少。IL-1β诱导的原代软骨细胞损伤在柚皮素的干预下得到逆转；这种逆转是剂量依赖性的。机制研究表明，柚皮素抑制了白细胞介素-1β刺激的原代细胞中的 toll 样受体 4（TLR4）/肿瘤坏死因子受体相关因子 6（TRAF6）/核因子-κB 通路，而 TLR4 激活剂 LPS 逆转了这种抑制作用。此外，建立了骨关节炎小鼠模型并用柚皮素进行治疗。结果表明，柚皮素减轻了小鼠骨关节炎的病理症状，降低了膝软骨组织中 TLR4 和 TRAF6 的表达以及 NF-κB 的磷酸化。它还抑制了炎症因子的分泌，减少了细胞外基质的降解，并降低了 cleaved caspase3 的蛋白表达。总之，这项研究的结果表明，柚皮素可能是治疗骨关节炎的一种潜在选择。
