Antioxidant in Green Tea Reverses Arthritis Symptoms in Rat Model

The green tea compound epigallocatechin-3-gallate (EGCG) was shown to effectively reverse the symptoms of adjuvant-induced arthritis (AIA) in a rat model, which mimics human rheumatoid arthritis (RA).

EGCG is the most abundant catechin in tea and is a potent antioxidant that may have therapeutic applications in the treatment of many disorders. It is found in green tea but not black tea.


In the current study, investigators at Washington State University (Spokane, USA) worked with cultures of IL-1beta (interleukin 1beta)–stimulated human RA synovial fibroblasts (RASFs) as well as with a rat model of adjuvant-induced arthritis (AIA).

Inhibition of the signaling proteins transforming growth factor beta–activated kinase 1 (TAK1), IL-1 receptor–associated kinase 1 (IRAK-1), and TNF receptor–associated factor 6 (TRAF6) was evaluated in cultures of IL-1beta–stimulated RASFs, some of which had been treated with EGCG. Western blotting, immunoprecipitation, and 20S proteasome assays were used to study the ubiquitination process in RASFs, and the efficacy of EGCG in regulating these processes in RASFs was evaluated. Molecular docking was performed to examine the interaction of EGCG with human TAK1, IRAK-1, and TRAF6. These findings were confirmed using a rat model of adjuvant-induced arthritis (AIA).

Results published in the February 2016 issue of the journal Arthritis and Rheumatology revealed that inhibition of TAK1, but not IRAK-1 or TRAF6, completely blocked IL-1beta-induced IL-6 and IL-8 synthesis in RASFs. EGCG inhibited TAK1 phosphorylation at one specific site and occupied a separate ATP-binding site to inhibit its kinase activity. EGCG pretreatment also inhibited autoubiquitination of TRAF6, a posttranslational modification essential for TAK1 autophosphorylation, by forming a stable hydrogen bond on TRAF6. Furthermore, EGCG enhanced proteasome-associated deubiquitinase expression to rescue proteins from proteasomal degradation. Preventing the tagging of proteins with ubiquitin saves them from destruction by the proteasome.

Western blot analyses of joint homogenates from EGCG-treated rats with AIA showed a significant increase in polyubiquitination, TAK1 phosphorylation, and TRAF6 expression when compared to naive rats. Administration of EGCG for 10 days reversed AIA in rats by reducing TAK1 phosphorylation and polyubiquitination.

"Existing drugs for rheumatoid arthritis are expensive, immunosuppressive, and sometimes unsuitable for long-term use," said senior author Dr. Salah-uddin Ahmed, associate professor of pharmaceutical sciences at Washington State University. "This study has opened the field of research into using EGCG for targeting TAK1—an important signaling protein—through which proinflammatory cytokines transmit their signals to cause inflammation and tissue destruction in rheumatoid arthritis."

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