Department of Orthopaedic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.
Department of Orthopaedic Surgery, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.
Oxid Med Cell Longev. 2022 Jul 8;2022:3047425. doi: 10.1155/2022/3047425. eCollection 2022.
Osteoarthritis (OA) is a common degenerative joint disease that may be closely linked to inflammation and oxidative stress destroying the balance of cartilage matrix. Theaflavin-3,3'-digallate (TFDG), a natural substance derived from black tea, has been reported to restrict the activity of inflammatory cytokines and effectively eliminate reactive oxygen species (ROS) in various diseases. However, it is not clear whether TFDG can improve OA.
Chondrocytes were treated with or without IL-1 and 20 M and 40 M TFDG. The effect of TFDG on the proliferation of chondrocytes was detected by CCK8. RT-qPCR was used to detect the gene expression of inflammatory factors, extracellular matrix synthesis, and degradation genes. Western blot and immunofluorescence assays were used to detect the protein expression. The fluorescence intensity of reactive oxygen species labeled by DCFH-DA was detected by flow cytometry. We established an OA rat model by performing destabilized medial meniscus (DMM) surgery to observe whether TFDG can protect chondrocytes under arthritis in vivo.
TFDG was found to inhibit proinflammatory factors (IL-6, TNF-, iNOS, and PGE) and matrix-degrading enzymes (MMP13, MMP3, and ADAMTS5) expression and protected extracellular matrix components of chondrocytes (ACAN, COL2, and SOX9). TFDG accelerated the scavenging of ROS caused by IL-1 according to the Nrf2 signaling pathway activation. At the same time, TFDG suppressed the PI3K/AKT/NF-B and MAPK signaling pathways to delay the inflammatory process. The cartilage of DMM rats receiving TFDG showed lower Osteoarthritis Research Society International (OARSI) scores and expressed higher levels of COL2 and Nrf2 compared with those of rats in the DMM group.
TFDG could protect cartilage from degradation and alleviate osteoarthritis in rats, which suggests that TFDG has potential as a drug candidate for OA therapy.
骨关节炎（OA）是一种常见的退行性关节疾病，可能与炎症和氧化应激破坏软骨基质平衡密切相关。茶黄素-3,3′-二没食子酸酯（TFDG）是一种从红茶中提取的天然物质，已被报道能抑制炎性细胞因子的活性，并能有效清除各种疾病中的活性氧（ROS）。然而，目前尚不清楚 TFDG 是否能改善 OA。
用或不用白细胞介素-1（IL-1）和 20μM 和 40μM TFDG 处理软骨细胞。CCK8 检测 TFDG 对软骨细胞增殖的影响。RT-qPCR 检测炎性因子、细胞外基质合成和降解基因的表达。Western blot 和免疫荧光检测蛋白表达。用 DCFH-DA 标记的活性氧荧光强度通过流式细胞术检测。通过进行不稳定内侧半月板（DMM）手术建立 OA 大鼠模型，观察 TFDG 能否在体内关节炎条件下保护软骨细胞。
TFDG 抑制促炎因子（IL-6、TNF-α、iNOS 和 PGE）和基质降解酶（MMP13、MMP3 和 ADAMTS5）的表达，并保护软骨细胞的细胞外基质成分（ACAN、COL2 和 SOX9）。TFDG 通过激活 Nrf2 信号通路加速清除由 IL-1 引起的 ROS。同时，TFDG 抑制 PI3K/AKT/NF-B 和 MAPK 信号通路，从而延缓炎症进程。与 DMM 组大鼠相比，接受 TFDG 治疗的 DMM 大鼠的软骨 OARSI 评分较低，COL2 和 Nrf2 表达较高。
TFDG 可保护软骨免受降解，缓解大鼠 OA，提示 TFDG 具有作为 OA 治疗药物候选物的潜力。
