Anti-inflammatory flavonoid inhibits cytokines that cause destruction of cartilage and bone in arthritis.

A new study from the University of Michigan Health System suggests that a flavonoid (a type of polyphenol) called EGCG extracted from green tea may provide therapeutic benefits to people with rheumatoid arthritis.

The NIH-sponsored study, presented April 29, 2007 at the Experimental Biology 2007 in Washington, D.C., looks at a potent anti-inflammatory phytochemical derived from green tea. Researchers found that the compound, named epigallocatechin -3- gallate (EGCG), an active principal of green tea extract, is a potent anti-inflammatory molecule, and also was able to inhibit production of interleukin-6 (IL-6) and prostaglandin E2, the inflammatory products found in the connective tissue of people with rheumatoid arthritis.

Synovial fibroblasts (cells that form a lining of synovial tissue surrounding the capsule of the joints) were isolated from the joints of the patients suffering from rheumatoid arthritis, cultured in growth medium, and incubated with EGCG. Synovial fibroblasts were then stimulated with pro-inflammatory cytokine IL-1ß, a protein of the immune system known to play an important role in causing joint destruction in rheumatoid arthritis.

In an earlier study published by Dr. Ahmed’s research group last fall, the researchers showed some interesting and novel findings when EGCG pretreated synovial fibroblasts were stimulated with the cytokine IL-1ß to study the protective effect of this green tea compound. Compared to untreated synovial fibroblasts, the cells treated with EGCG markedly blocked IL-1ß’s ability to produce the proteins and enzymes that infiltrate the joints of persons with rheumatoid arthritis causing cartilage degradation.

The scientists decided to extend their study to see if the green tea compound also has the capability to block the activity of two other potent molecules, IL-6 and cyclooxygenase-2 (COX-2), actively involved in causing bone erosion in the RA joint. In the new study presented at Experimental Biology, the scientists once again isolated synovial fibroblasts taken from the joints of patients suffering from rheumatoid arthritis and incubated these cells with the green tea compound. When untreated cells were stimulated with IL-1ß, a sequence of molecular events occurred that resulted in production of the bone-destructive molecules. But the scientists found that pre-incubation with EGCG was capable of blocking the production of these molecules in a dose-dependent manner. Furthermore, EGCG also inhibited the production of prostaglandin E2, which causes inflammation in the joints.

The cell signaling pathways that regulate levels of these immune system molecules under both normal and rheumatoid arthritis situations is well established, and the researchers were able to trace the effects of the green tea compound infusion to see that it worked by inhibiting these pathways.

Dr. Ahmed says that these studies suggest that EGCG or molecules that could be derived synthetically from the EGCG found in green tea may be of therapeutic value in inhibiting the joint destruction in this challenging disease. The laboratory now is focused on the inhibitory role of EGCG in gene expression. The scientists plan to give EGCG orally to mice genetically bred to be animal models of rheumatoid arthritis to see if it provides similar therapeutic or preventive effects. Dr. Ahmed believes these studies will form a strong foundation for future testing of green tea flavonoids in humans with rheumatoid arthritis (Courtesy of EurekAlert!, a service of AAAS).

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