Theaflavin-3,3′-Digallate Protects Cartilage from Degradation by Modulating Inflammation and Antioxidant Pathways

BACKGROUND: 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. METHODS: Chondrocytes were treated with or without IL-1β and 20 μM and 40 μM 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. RESULTS: TFDG was found to inhibit proinflammatory factors (IL-6, TNF-α, 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-1β according to the Nrf2 signaling pathway activation. At the same time, TFDG suppressed the PI3K/AKT/NF-κB 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. CONCLUSION: TFDG could protect cartilage from degradation and alleviate osteoarthritis in rats, which suggests that TFDG has potential as a drug candidate for OA therapy.