Several years ago, German researchers discovered that a traditional European herbal remedy for rheumatism, nettle leaf extract, inhibits TNF-alpha and IL-1 beta.

It is interesting to note that the prescription drug Enbrel®, approved for the treatment of rheumatoid arthritis, acts by suppressing TNF-alpha.

One of the ways nettle leaf extract blocks proinflammatory signaling is by inhibiting the genetic transcription factor that activates TNF-alpha and IL-1 beta in synovial tissue.  This proinflammatory transcription factor, known as nuclear factor kappa beta (NF-kb), is elevated in chronic inflammatory diseases and is essential to activation of TNF-alpha. Nettle is thought to work by preventing degradation of the natural inhibitor of NF-kb in the body. TNF-alpha also activates NF-kb in synovial cells, leading to the suggestion that a cycle of cross-activation between TNF-alpha and NF-kb may sustain and amplify the disease process in rheumatoid arthritis.

A recent laboratory experiment revealed one of the mechanisms by which nettle leaf extract protects joints. Inflammatory joint diseases are characterized by breakdown of the extracellular matrix (ECM), which surrounds and supports cells. In arthritis, TNF-alpha and especially IL-1 beta stimulate enzymes known as matrix metalloproteinases (MMP’s) that break down the extracellular matrix. The experiment measured MMP levels of chondrocytes (joint cells) exposed to IL-1 beta. Nettle leaf extract was found to significantly inhibit all the matrix metalloproteinases tested (MMP-1, -3 and -9).

Another study conducted on 40 patients suffering from acute arthritis compared the effects of 200 mg of the nonsteroidal anti-inflammatory drug (NSAID) diclofenac with 50 mg of the NSAID in combination with 50 g of stewed nettle leaf per day.  Total joint scores improved significantly in both groups by approximately 70%. The nettle leaf extract clearly enhanced the anti-inflammatory effect of the NSAID. The addition of nettle extract made possible a 75% dose reduction of the NSAID, while still retaining the same anti-inflammatory effect with reduced side effects.

Nettle leaf extract thus makes the ideal complement to COX-2 inhibitors, by virtue of its ability to counteract their negative effects. The herbal COX-2 inhibitor Nexrutine® is derived from the bark of the phellodendron tree, which folk healers use to treat arthritis and other ailments. Prescription COX-2 inhibitors intervene in the inflammation cascade by blocking the action of the COX-2 enzyme. But Nexrutine® inhibits the gene expression of COX-2, preventing its manufacture in the first place. This difference in mechanism of action may account for the rapidity of Nexrutine®’s inflammation-quenching action. According to reports from subjects who used Nexrutine® for two weeks, 79% agreed that Nexrutine® helped relieve or avoid the general aches and pains associated with overexertion and physical activity. No side effects were reported at recommended dosages.