Theaflavin-3,3${}^{\prime }$-Digallate Protects Cartilage from Degradation by Modulating Inflammation and Antioxidant Pathways

Abstract

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.

Ganoderic acid A slows osteoarthritis progression by attenuating endoplasmic reticulum stress and blocking NF‐Κb pathway

“…Eighteen male C57 mice (8 weeks old, weighing between 18 and 22 g) were purchased from the Experimental Animal Center of Nanchang University and housed in a dark/light cycle environment at 20–25°C, with open water and food access. To establish an animal OA model, Destabilized medial meniscus (DMM) (Lin et al., 2022; Teng et al., 2022) surgery took place under pentobarbital anesthesia. By taking the control group as the sham group, the joint capsule was incised without damaging the cartilage and meniscus, while the joint cavity was injected with PBS equal to GAA every week.…”

Osteoarthritis in the Elderly Population: Preclinical Evidence of Nutrigenomic Activities of Flavonoids

“…They have a 3-hydroxyflavone backbone, and they offer several benefits for various pathologies, particularly those with an inflammatory etiology. Two molecules, Epigallocatechin-3-O-gallate (EGCG) and Theaflavin-3,3’-Digallate (TFDG), have been studied in two manuscripts [ 41 , 42 ]. In Yang et al (2022a), it was found that EGCG could alleviate chondrocyte injury, as mimicked in vitro by treating the CHON-001 cell line with IL-1β, reducing MMP-13 and IL-6 expression and release.…”

“…EGCG’s activities appear to be associated with decreased levels of the microRNA miR-29b-3p, which targets phosphatase and tensin homolog (PTEN) mRNA, and then increases its expression, as indicated by the reversal of EGCG activities by MiR-29b-3p mimic. Further confirmation was provided by PTEN overexpression, which showed that it could abrogate the effects of miR-29b-3p mimics in IL-1β-treated CHON-001 cells, highlighting the known nutrigenomic effect of EGCG [ 41 ]. TFDG, a natural compound found in black tea, was found to increase the proliferation of IL-1β-treated chondrocytes, as well as increase ECM deposition (ACAN and Col-II) and reduce ECM degradation (decrease in MMP-13, MMP-3, and ADAMTS5).…”

Theaflavin-3,3'-Digallate Protects Liver and Kidney Functions in Diabetic Rats by Up-Regulating Circ-ITCH and Nrf2 Signaling Pathway

“…Recent research has revealed that circ-ITCH (hsa_circ_0001141: circular RNA itchy E3 ubiquitin protein ligase) can modulate the nuclear factor erythroid-derived 2-related factor 2 (Nrf2) pathway to inhibit oxidative stress and improve diabetic complications . Although TFDG has been shown to regulate the Nrf2 pathway in some previous studies, , the effect of TFDG on circRNA has been less well studied. In the current research, we delve deeper into the function of circ-ITCH in diabetic liver and kidney injury and in the activation of the Nrf2 pathway regulated by TFDG.…”