Vendor Workshop Sponsored by Metagenics, Inc. ~
Gastrointestinal toxicity of non-steroidal anti-inflammatory drugs (NSAIDs) is well documented, and a primary drawback in their long-term use. A common theme of NSAIDs efficacy is their non specific targeting of clycooxygenase (COX) enzymes resulting in inhibition and subsequent reduction in Prostaglandin H2 (PGH2) inflammatory derived eicosanoids. While inhibition of inflammatory cell (e.g., macrophage) COX enzyme activity to reduce PGH2 is desired, gastrointestinal cell COX enzyme inhibition is not, and results in the inability of GI cells to repair damage leading to ulceration and GI toxicity. In pursuit of a safer naturally derived anti-inflammatory agent, we designed a program to assess natural agents for selective and balanced Cox 2 vs. Cox 1 inhibition, and therefore anti-inflammatory efficacy with predicted low GI toxicity. Greater then 100 natural DSHEA ingredients with a history of safe use were screened for anti-inflammatory activity in an in vitro system. Top candidates were then screened in an in vitro GI toxicity model system. The most effective natural product derived from this process was an optimized ratio of hop (Humulus lupulus) and rosemary (Rosmarinus officinalis) constituents. When compared to 5 other common DSHEA products on a weight/weight basis it had superior selective Cox1/2 activity. Human clinical ex-vivo studies demonstrate that this product effectively confers anti-inflammatory activity within one hour of ingestion and corresponding with dose. Effectiveness in human clinical studies to treat various inflammatory conditions will be discussed.