New Mechanism of Action of NSAIDs Found

Non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen and aspirin are widely used to treat pain and inflammation. But even at similar doses, different NSAIDs can have unexpected and unexplained effects on many diseases, including heart disease and cancer. 

A new study published in the journal Immunity, led by Yale, uncovered a previously unknown process with NSAIDs affecting the body. The new mechanism found differs from previously known ones by which NSAIDs decrease inflammation. 

NRF2 New Mechanism 

The research team found that only some NSAIDs, like indomethacin, for example, activate a protein called nuclear factor erythroid 2-related factor 2, or NRF2, which triggers anti-inflammatory processes in the body. 

Several clinical trials are evaluating whether NRF2-activating drugs are effective in treating inflammatory diseases like Alzheimer’s disease, asthma, and various cancers; this research could inform the potential and limitations of those drugs.

The new mechanism of action might lead to a more effective prescription of NSAIDs going forward, with NRF-activating NSAIDs and non-NRF2-activating NSAIDs applied to the diseases they’re most likely to treat. 

This protein has been found to be involved in different processes, including metabolism, immune response, and inflammation, while also being implicated in aging and longevity. 


Yale University. “New research may explain unexpected effects of common painkillers.” ScienceDaily. ScienceDaily, 23 May 2022.

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