Anti-Inflammatory Screening Strategy
DermaMedics scientists have identified the inflammatory markers (cytokines) produced by skin and immune cells that are important in the development of various inflammatory skin problems, such as psoriasis and atopic dermatitis. A typical cutaneous inflammatory response and the key cytokines and adhesion molecules expressed during this reaction are illustrated here.
The inflammatory reaction begins with an initial insult to the skin, which results in the release of inflammatory cytokines by keratinocytes and fibroblasts. These cytokines then stimulate endothelial cells to express adhesion molecules, which aid in the attachment and transmigration of immune cells into the area of inflammation. Once the immune cells have entered the area of insult, the inflammatory response is perpetuated until the insult and damage caused is resolved. The inhibition of the expression of one or more of these cytokines or adhesion molecules during an inflammatory response can result in a reduction or inhibition of inflammation.
The screening of a candidate molecule’s ability to reduce the production of these key inflammatory markers occurs in a four step process as follows:
- The effect of a drug candidate on the production of inflammatory cytokines and adhesion molecules produced by keratinocytes, fibroblasts and monocytes (ELISA) is assessed first.
- The effect of drug candidate on the gene expression of key inflammatory cytokines in keratinocytes, fibroblasts and monocytes (RT-PCR) is determined.
- The drug candidates ability to alter the gene expression of key adhesion molecules produced by endothelial cells is determined using RT-PCR technology.
- The effect of a drug candidate on the production of other important inflammatory cytokines is determined by use of Antibody Arrays.
This anti-inflammatory screening strategy is illustrated here.
The Anti-Inflammatory Therascreen allows for the determination of the effect a bioactive would have during an inflammatory condition.
By carrying out this rigorous TheraScreen analysis for anti-inflammatory drug candidates, DermaMedics scientists were able to identify a naturally occurring low molecular weight compound, Therosol®, which had broad anti-inflammatory activities. The various inflammatory processes that this compound can inhibit, either directly (blue X) or indirectly (red X) are shown here.
Therosol® is a small phenolic compound that is found in a variety of plants. Because of its fragrance and taste, it has been used as a flavoring agent in foods for many years. As a result, the Health and Human Services, through its National Toxicology Program, has done an exhaustive amount of safety testing on Therosol®. The compound has been proven to be safe for both oral and skin use. Therosol® is in all DermaMedics products.