New activity for anti-inflammatory drugs

New activity for anti-inflammatory drugs | National Institutes of Health (NIH) | Mar 2017

Scientists sometimes find novel uses for old drugs. For example, the common pain reliever aspirin is now used by millions of people to help prevent heart attack, stroke, or certain cancers.

Aspirin is a type of non-steroidal anti-inflammatory drug (NSAID). Because aspirin has found multiple uses, other NSAIDs might also have health benefits that haven’t yet been discovered.

Aspirin and other NSAIDs are known to have anti-inflammatory effects by inhibiting COX (cyclooxygenase) enzymes. These enzymes are pivotal in the inflammatory process. 

A research team led by Dr. Hang Hubert Yin of the University of Colorado, Boulder, and the BioFrontiers Institute used high-throughput screening to test nearly 1,300 FDA-approved drugs for anti-inflammatory activity.

The team focused on another group of enzymes called caspases that are known to be important for inflammation and thus might also serve as useful therapeutic targets.

The team first ranked the drugs by their ability to inhibit the activity of the caspase-4 enzyme. They found 27 compounds that inhibited caspase-4 activity to less than 25%. Of these, about half—and 8 of the top 10 most potent—were NSAIDs. Further tests of 9 selected NSAIDs showed that all except aspirin inhibited multiple caspases.

In human cells, the caspases were inhibited by the same NSAIDs in the same rank order as in the high-throughput screen.

  • Fenbufen and indoprofen were the strongest inhibitors;
  • naproxen and ibuprofen were weak inhibitors; and
  • aspirin was ineffective.

In additional experiments, the team found that the NSAID inhibition of caspase was independent of COX enzymes

Caspases are known to play a role in inflammatory diseases such as rheumatoid arthritis and heart disease. This newly discovered mechanism of NSAID activity suggests future studies into how these drugs affect caspases in the human body. The results could inform strategies to fight inflammation with fewer side effects.

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